Phytopathogenic fungi can weaken the effectiveness of antifungal chemicals from plants and artificial synthesis through a xenobiotic detoxification system.Nevertheless,the transcription factors responsible for transcr...Phytopathogenic fungi can weaken the effectiveness of antifungal chemicals from plants and artificial synthesis through a xenobiotic detoxification system.Nevertheless,the transcription factors responsible for transcriptional activation of xenobiotic detoxification genes in phytopathogenic fungi are rarely reported.Here,we show that a GATA transcription factor,SsGATA1,regulates the transcription of drug efflux pump genes,thus contributing to tolerance to various types of chemical fungicides,including propiconazole,caspofungin,and azoxystrobin in Sclerotinia sclerotiorum.Similarly,SsGATA1 also confers tolerance to isothiocyanate and flavonols,two compounds reported as broad-spectrum antifungal chemicals,by mediating the transcription of the isothiocyanate hydrolase SsSaxA.Importantly,SsGATA1 positively regulates pathogenicity,which is attributed to the upregulation of hydrolases and SsSaxA during infection.Furthermore,SsGATA1 is responsible for tolerance to several stresses.Our findings demonstrate that SsGATA1 plays roles in multidrug resistance and pathogenicity by activating the transcription of hydrolases and xenobiotic detoxification genes.展开更多
Neuronal cells require precise and stable control of gene expression throughout their extended lifespan,which presents numerous challenges for gene transcription.While traditional studies of transcriptional regulation...Neuronal cells require precise and stable control of gene expression throughout their extended lifespan,which presents numerous challenges for gene transcription.While traditional studies of transcriptional regulation have primarily focused on canonical DNA-binding factors,there is an increasing recognition of the role of regulatory RNAs and RNA-binding proteins(RBPs)in modulating this process.展开更多
Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research a...Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research area.However,the transcriptional regulatory mechanisms underlying monoterpenoid synthesis in Z.bungeanum remain unclear,hindering these breeding efforts.In this study,RNA sequencing,gas chromatography–mass spectrometry,and other molecular biology techniques were used to identify the underlying transcriptional regulation mechanisms.Two transcription factors,ZbbHLH2 and ZbERF6,were identified as key regulators of monoterpenoid synthesis in Z.bungeanum that upregulate various monoterpenoid synthesis-associated genes and are novel transcriptional activators of ZbIDI,which encodes the rate-limiting enzyme in plant monoterpenoid synthesis.Functional analysis revealed that the expression of three genes[1]modulates monoterpenoid accumulation in Z.bungeanum peel.These findings provide novel insights into the metabolic regulatory network of monoterpenoid synthesis in Z.bungeanum peel,offer potential strategies for the biofortification of specific monoterpenoids,and will promote the development of Z.bungeanum germplasm for targeted breeding and quality improvement.展开更多
Sugars are crucial in determining fruit quality and significantly affect the commercial value.Sucrose is the primary soluble sugar in ripe peach fruit.However,the regulatorymechanism of sucrose synthesis in peach frui...Sugars are crucial in determining fruit quality and significantly affect the commercial value.Sucrose is the primary soluble sugar in ripe peach fruit.However,the regulatorymechanism of sucrose synthesis in peach fruit,especially during natural ripening,remains largely unexplored.This study identified two structural genes of peach(Prunus persica,‘Jinlinghuanglu’),PpSUS1 and PpSPS2,whose expression was strongly correlated with sucrose accumulation.The transcription factors that regulated the expression of these two genes during peach fruit ripening were screened;and three NACs(NAM,ATAF1/2 and CUC2),whose expression also significantly correlated with sucrose accumulation,were identified.Notably,PpNAP4(NAC-like,activated by APETALA3/PISTILLATA)displayed the highest activation activity toward the PpSUS1 and PpSPS2 promoters.The direct binding activity was confirmed using luciferase imaging and electrophoretic mobility shift assays.The sucrose content and expression of sucrose synthesis-related genes significantly increased when PpNAP4 was overexpressed in peach fruit and the tomato nor mutant.Moreover,PpNAP4 functioned synergistically with PpNAP6 to modulate sucrose synthesis,and PpNAP4 targeted its own promoter and feedback-activated its own expression.This research unveils a novel regulatory mechanism controlling sucrose accumulation in peach fruit.展开更多
Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the reg...Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.展开更多
Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and pos...Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and post-transcriptional steps of gene expression.Then,after further analysis of the literature,we report evidence that,not strictly limited to neurodevelopmental effectors,such pleiotropy also applies to other transcription factors,involved in physiology and homeostasis.Furthermore,through the systematic analysis of a major public protein-protein interaction database,we gather strong evidence that the involvement of“canonical”transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon,characterizing hundreds of effectors.Finally,we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario.展开更多
Pigment biofortification in rice,particularly through enhanced anthocyanin accumulation,is increasingly recognized in Asia for its potential to improve nutritional quality and antioxidant capacity while addressing reg...Pigment biofortification in rice,particularly through enhanced anthocyanin accumulation,is increasingly recognized in Asia for its potential to improve nutritional quality and antioxidant capacity while addressing regional health challenges.However,the regulatory network underlying anthocyanin biosynthesis in rice remains incompletely characterized,especially regarding MYB transcription factors that may control pigment accumulation in diverse germplasm.In this study,a genome-wide analysis of MYB transcription factors in Oryza sativa subsp.japonica identified 109 OsMYB genes.Phylogenetic comparison with known anthocyanin regulators from Arabidopsis thaliana and Oryza rufipogon revealed conserved clades containing potential pigment-related regulators.Integrative analyses including gene structure,conserved motif identification,promoter cis-element profiling,and miRNA target prediction were conducted to explore their regulatory potential.Expression profiling during grain development in black and mixed rice identified 32 OsMYB genes as potential candidates associated with anthocyanin accumulation.Promoter analysis revealed enrichment of light-responsive,stress-responsive,and developmental regulatory elements,suggesting coordinated regulation by environmental and developmental signals.Predicted interactions with several Osa-miRNAs further indicate potential post-transcriptional control of these genes.Among the candidates,OsMYB65 showed strong differential expression in pigmented rice grains and possessed multiple regulatory elements associated with anthocyanin biosynthesis,highlighting it as a promising regulator.Overall,this integrative genome-wide analysis identifies a prioritized set of MYB transcription factors that may regulate anthocyanin biosynthesis in rice,providing valuable targets for functional validation and pigment-oriented crop improvement.展开更多
Autophagy is a highly conserved intracellular recycling process in eukaryotes that delivers cellular components to the lysosome or vacuole for degradation,thereby maintaining intracellular homeostasis.Acting as a qual...Autophagy is a highly conserved intracellular recycling process in eukaryotes that delivers cellular components to the lysosome or vacuole for degradation,thereby maintaining intracellular homeostasis.Acting as a quality control system,autophagy plays a pivotal role in plant growth,development,and adaptation to environmental challenges.The regulation of autophagy under stress conditions involves multi-layered mechanisms,including transcriptional,epigenetic,and post-translational controls.Transcription factors from families such as WRKY,NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON(NAC),and basic leucine zipper(bZIP)directly bind to the promoters of autophagy-related(ATG)genes,thereby integrating stress-responsive signal pathways to orchestrate autophagic activity dynamically.Epigenetic modifications,including histone modifications,DNA methylation,N6-methyladenosine(m6A)methylation,and microRNA-mediated silencing,further fine-tune expression of ATG genes in response to changing environments.At the post-translational level,modifications such as phosphorylation,ubiquitination,acetylation,persulfidation,and S-nitrosylation serve as rapid regulatory switches that modulate autophagosome formation under stress.This review summarizes recent advances in elucidating these regulatory layers,highlighting how these regulators collectively modulate autophagy to improve plant tolerance to environmental cues.Unraveling these mechanisms will expand our understanding of the autophagy regulatory network in plants and provide potential strategies for improving stress tolerance in crops.展开更多
Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playin...Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.展开更多
The HD-ZIP gene family,a group of plant-specific transcription factors,plays pivotal regulatory roles in various aspects of plant growth and development.Accumulating evidence has demonstrated the extensive involvement...The HD-ZIP gene family,a group of plant-specific transcription factors,plays pivotal regulatory roles in various aspects of plant growth and development.Accumulating evidence has demonstrated the extensive involvement of HD-ZIP members in regulating reproductive developmental processes.This review systematically summarizes both the structural characteristics of the four HD-ZIP subfamilies(Ⅰ-Ⅳ)and their distinct regulatory roles in plant reproductive development.Recent studies reveal that a conserved HD-ZIPⅠclade serves as a core regulator of key reproductive processes,ranging from spike development in monocots(e.g.,barley Vrs1 and maize GT1)to sex determination in dicots(e.g.,cucumber CmHB40 and persimmon MeGI).Meanwhile,members of other subfamilies(HD-ZIPⅡ-Ⅳ)contribute significantly to diverse reproductive processes including pistil development,floral organ formation,and anther development,among others.This review provides a comprehensive synthesis of HD-ZIP subfamily functions in reproductive development,integrating current knowledge while highlighting critical research gaps.These insights aim to provide theoretical foundations for functional characterization and potential applications of HDZIP reproductive regulators,while advancing our understanding of transcriptional regulation mechanisms in plant reproductive development.展开更多
Alzheimer's disease is characterized by hippocampal neuronal apoptosis,which leads to cognitive decline.The pathophysiology of Alzheimer's disease is largely driven by disrupted cellular metabolism and insuffi...Alzheimer's disease is characterized by hippocampal neuronal apoptosis,which leads to cognitive decline.The pathophysiology of Alzheimer's disease is largely driven by disrupted cellular metabolism and insufficient neuronal energy supply.However,current treatments for Alzheimer's disease remain limited because of side effects and disease complexity.Increasing evidence suggests that amyloid-βoligomer-induced neuronal insulin resistance and metabolic dysfunction play key roles in Alzheimer's disease progression,yet their underlying mechanisms and therapeutic strategies remain unclear.In this translational preclinical study,we combined a case-control analysis,in vitro cell assays,and in vivo experiments using amyloid precursor protein/presenilin 1 transgenic mice to investigate whether transcriptional regulation of key regulatory factors restores neuronal energy supply and improves Alzheimer's disease-induced pathology.The case-control analysis identified pre-B-cell leukemia transcription factor 1 as a crucial regulator of brain metabolic homeostasis in Alzheimer's disease.We developed a blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein to enhance pre-B-cell leukemia transcription factor 1 expression,with the aim of restoring neuronal energy supply and reducing apoptosis.Mechanistic investigations using Alzheimer's disease models revealed that pre-B-cell leukemia transcription factor 1 transcriptionally upregulates insulin receptor substrate 1 by interacting with its promoter,which resulted in augmented insulin signaling.Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 downregulated PDK4,significantly upregulated the expression of pyruvate dehydrogenase,and promoted mitochondrial oxidative phosphorylation activity,which inhibited the abnormally enhanced glycolytic flux,increased adenosine triphosphate production,and ultimately helped restore neuronal energy homeostasis.Therapeutic administration of trans-activator of transcription-pre-B-cell leukemia transcription factor 1 in amyloid precursor protein/presenilin 1 transgenic mice significantly enhanced cognitive performance,diminished hippocampal neuronal apoptosis,and mitigated amyloid-βdeposition.No significant hepatotoxicity,nephrotoxicity,or other detectable adverse effects were observed within the dose ranges and time windows of administration.Taken together,we identified pre-B-cell leukemia transcription factor 1 as a crucial transcriptional regulator of neuronal energy metabolism in Alzheimer's disease.Moreover,we elucidated the molecular mechanism through which the pre-B-cell leukemia transcription factor 1-insulin receptor substrate 1 signaling axis sustains metabolic homeostasis.Furthermore,we demonstrated that the blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein constitutes a mechanistically innovative and highly translatable therapeutic strategy for Alzheimer's disease.展开更多
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism...Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.展开更多
As the abundant phenolic substance in peach fruit,chlorogenic acid(CGA)has various biological activities and is an important target for improving the nutritional and resistance qualities.Nevertheless,the gene function...As the abundant phenolic substance in peach fruit,chlorogenic acid(CGA)has various biological activities and is an important target for improving the nutritional and resistance qualities.Nevertheless,the gene functions and regulatory mechanisms of CGA biosynthesis in peach fruit are poorly understood.Using gene expression patterns from different developmental stages and different peach cultivars,one structural gene PpHCT5 was identified as being involved in CGA biosynthesis.An in vitro enzyme activity assay confirmed that the PpHCT5 protein catalyzed the biosynthesis of caffeoyl CoA and quinic acid into CGA.The in vivo functional validation confirmed that PpHCT5 overexpression increased CGA accumulation in transgenic plants,including peach,tomato,and tobacco.Furthermore,upstream transcription factors of PpHCT5 were identified.PpMYB62 and PpbHLH14 activated PpHCT5 expression by directly binding promoter MBS or G-box elements,thereby inducing CGA accumulation in peach fruit.Additionally,PpMYB308 interactions with PpbHLH14 promoted the activating effect of PpbHLH14 on PpHCT5,thereby positively regulating CGA biosynthesis.Thus,a regulatory network of PpMYB and PpbHLH transcription factors to modulate the PpHCT5-mediated CGA biosynthesis pathway was constructed.It will be useful for elucidating the complex mechanisms underlying CGA biosynthesis and provide a theoretical basis for the development of resistance and increased CGA content breeding in peach.展开更多
Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways ...Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.展开更多
Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,wh...Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,while little is known about the negative regulators.CRISPR/Cas9 gene-editing technology,with the advantage of precise genetic modification,is a desirable tool for breeding biofortified materials and exploring potential molecular mechanisms.In this study,a transcriptional repressor,Sl MYB32,was characterized in tomato fruit.Phenotype and metabolomic analyses confirmed that knockout of Sl MYB32 resulted in increased accumulation of flavonols and flavanones,especially about 1 mg g-1FW of quercetin 3-O-rutinoside(rutin).Transcriptome analysis indicated that expression of key genes Sl PAL6,Sl4CL3 and Sl4CL4 as well as five candidate Sl UGTs were significantly up-regulated in slmyb32 mutants.Dual-luciferase and EMSA assays indicated Sl MYB32 could bind to and repress promoter activities of Sl PAL6 and Sl4CL3.Expression of 27 transcription factors belonging to 12 families was significantly changed in slmyb32 mutants,among which two Sl MYBs,two Sl NACs,two Sl AP2s and one Sl WRKY were clustered with known flavonoid regulators.Our results provide new insights into improving bioactive compounds in fruit and understanding negative regulatory mechanisms in flavonol and flavanone biosynthesis.展开更多
Starch is the most abundant accumulated substance in the grains of sorghum(Sorghum bicolor),the 5th most world-widely cultivated cereal crop,and is widely used by humans,especially in the direction of brewing in China...Starch is the most abundant accumulated substance in the grains of sorghum(Sorghum bicolor),the 5th most world-widely cultivated cereal crop,and is widely used by humans,especially in the direction of brewing in China.However,there are currently few reports on the starch biosynthesis regulatory mechanism in sorghum grains.Here,we employed RNA-seq and ATAC-seq strategies to discover the transcriptional regulation network responsible for starch biosynthesis in sorghum grains.Our results profiled all mRNAs in the sorghum grains at nine development stages covering the inflorescence,and grains from 3 to 30 days after pollination(DAP).Analysis of the gene sets determined temporal programs of gene expression,including thousands of transcription factor(TF)genes.We found a close correlation between the sequentially expressed gene sets and distinct cellular and metabolic programs of the developing grains.The cis-elements serving as binding sites of multiple TFs were identified via a comparative ATAC-seq assay.Cis-elements capable of binding TFs were also identified within the promoter regions of starch biosynthesis related genes(SBRGs).Moreover,the NAC family TF of SbNAC68 highly expressed in developing grains and demonstrated co-expression patterns with SBRGs.Furthermore,SbNAC68 was confirmed to bind to 5′-ACGCAA-3′,a typical motif of binding site for the TFs from NAC family,to affect the promotor activities of SBRGs and regulate their transcriptions.Collectively,through multiply omics strategies and the case dissection of SbNAC68,the present study provides molecular insights of transcriptional regulations into starch biosynthesis in sorghum grains.展开更多
Backgrounds:Triple-negative breast cancer(TNBC)is highly aggressive,insensitive to radiotherapy,and exhibits increased cancer stem cell(CSC)properties,contributing to poor patient outcomes.B-cell lymphoma 2(BCL2)assoc...Backgrounds:Triple-negative breast cancer(TNBC)is highly aggressive,insensitive to radiotherapy,and exhibits increased cancer stem cell(CSC)properties,contributing to poor patient outcomes.B-cell lymphoma 2(BCL2)associated transcription factor 1(BCLAF1)is an oncogene in certain cancers,but its role in TNBC is unclear.This study investigated BCLAF1’s involvement in radioresistance and CSC activity in TNBC.Methods:BCLAF1 expression and clinical significance were analyzed using The Cancer Genome Atlas(TCGA)breast cancer dataset.Radioresistant MDA-MB-231 cells were used to examine BCLAF1’s function.Proto-oncogene SRC(SRC)overexpression,BCLAF1 knockdown,dasatinib treatment,and hypoxia inducible factor 1 subunitα(HIF-1α)inhibition were employed to elucidate regulatory mechanisms.CSC activity was assessed using tumorsphere formation assays.Results:Elevated BCLAF1 mRNA levels were associated with advanced pathological and T stages(analysis of variance[ANOVA],p=1.4×10−3)and poorer overall survival by Kaplan–Meier analysis(p=0.021).BCLAF1 expression was positively correlated with SRC signaling pathway-associated genes,including Kirsten rat sarcoma viral oncogene homolog(KRAS),GTPase-activating protein-binding protein 1(G3BP1),and phosphoinositide-3-kinase regulatory subunit 1(PIK3R1).Radioresistant cells exhibited higher BCLAF1 expression.SRC overexpression reduced radiosensitivity,while increasing BCLAF1 levels.BCLAF1 knockdown suppressed tumorsphere formation.Dasatinib decreased BCLAF1,HIF-1α,and stemness proteins,including octamer-binding transcription factor 4(OCT-4),Notch intracellular domain(NICD),and cellular myelocytomatosis oncogene(c-Myc).BCLAF1 knockdown diminished nuclear HIF-1α,and HIF-1αinhibition abrogated BCLAF1-induced tumorsphere formation.Conclusions:BCLAF1 enhances radioresistance and CSC properties in TNBC via SRC-HIF-1αsignaling,suggesting that BCLAF1 is a potential therapeutic target to overcome radioresistance in TNBC.展开更多
Photosynthesis fuels crop growth and yield,yet the regulatory networks coordinating photosynthetic gene expression with carbon allocation remain incompletely understood.Here,we construct a gene regulatory network(GRN)...Photosynthesis fuels crop growth and yield,yet the regulatory networks coordinating photosynthetic gene expression with carbon allocation remain incompletely understood.Here,we construct a gene regulatory network(GRN)for rice photosynthesis by integrating time-resolved RNA-seq,ATAC-seq,and promoter cis-element analyses.We identify nine hub transcription factors(TFs),four of which(OsPIL13,OsbZIP72,OsCGA1,and OsGLK1)exhibit strong leaf-specific,light-inducible expression patterns.Overexpression of OsPIL13,OsbZIP72,or OsGLK1 using photosynthetic tissue-specific promoters significantly enhanced the light-saturated photosynthetic rate(Asat)across developmental stages,with OsPIL13 overexpression increasing Asat by up to 57%during grain filling.While several hub TFs boosted photosynthetic capacity,consistent improvements in biomass and grain yield under field conditions were rare.Notably,OsGLK1 overexpression confers stable yield gains across multiple growing seasons.Comparative transcriptomic analysis indicates that OsGLK1 also upregulates genes involved in brassinosteroid biosynthesis and sugar and lipid transporter genes,potentially linking photosynthetic output to growth and resource allocation.Collectively,our findings indicate that enhancing photosynthesis alone is insufficient to guarantee yield improvement;rather,the coordinated regulation of photosynthetic capacity and downstream carbon utilization is essential for sustainable productivity gains in rice.展开更多
Plant height is critical for crops in agricultural research and practice.Optimizing plant height helps to increase yield and lodging resistance.The green revolution gene semi-dwarf 1(SD1)encoding GA 20-oxidase 2(GA20o...Plant height is critical for crops in agricultural research and practice.Optimizing plant height helps to increase yield and lodging resistance.The green revolution gene semi-dwarf 1(SD1)encoding GA 20-oxidase 2(GA20ox2)has been widely used in modern rice breeding.However,the molecular mechanism of how SD1 is transcriptionally regulated remains elusive.TCP proteins,one family of the plantspecifictranscription factors(TFs),have been proved to widely distribute in plants and play important roles in plant growth and development.Here,we report a TCP TF OsTCP4,which belongs to class I clade TCP,plays critical roles in regulating plant height of rice through acting as a transcriptional repressor of SD1.OsTCP4 is a nuclear-localized TF,which has a preferential transcriptional accumulation in stem nodes and tiller bases.ostcp4 knock-out mutants displayed higher plant height compared with WT,while overexpression of OsTCP4 reduced plant height compared with WT,which was confirmedby two cultivars on four planting sites of Yunnan under three-year investigation.The expression of SD1 was upregulated in ostcp4 mutants and reduced in OsTCP4-overexpression plants.Moreover,OsTCP4 protein directly binds to the promoter region of SD1.The genetic regulation between OsTCP4 and SD1 was further verifiedwith ossd1 tcp4 double mutant.Moreover,distinction of plant height in ostcp4 lines and OsTCP4-OE lines is caused by different concentrations of GA1.Taken together,OsTCP4 acts as a transcriptional repressor of SD1 and it may play a critical role in rice growth and development through the fine-tuningof GA1 biosynthesis.展开更多
Tomato(Solanum lycopersicum),one of the world's most economically and nutritionally important crops,faces increasing challenges from abiotic stresses such as drought,salinity,and temperature extremes,which are bei...Tomato(Solanum lycopersicum),one of the world's most economically and nutritionally important crops,faces increasing challenges from abiotic stresses such as drought,salinity,and temperature extremes,which are being exacerbated by climate change.Understanding the molecular mechanisms underlying tomato's adaptation to these environmental constraints is essential for identifying stress-resilient genes and achieving sustainable production.This review synthesizes recent progress in elucidating the transcriptional and signaling responses of tomato to major abiotic stresses.Such stresses induce a series of physiological disorders,including osmotic imbalance,membrane damage,photosynthetic inhibition,and oxidative stress.Complex signal transduction networks mediate the perception and response to these stresses,involving second messengers,diverse protein kinases,and multiple phytohormones.These signaling pathways converge to orchestrate transcriptional reprogramming through the coordinated activity of various transcription factors,which modulate downstream genes to enhance antioxidant defense,osmotic adjustment,and ion homeostasis.Despite significant progress,substantial knowledge gaps remain regarding signal cross-talk and the integration of responses under compound stresses.Advances in multi-omics technologies are accelerating the identification of key stress-responsive genes,proteins,and metabolites,offering new opportunities for molecular breeding.Furthermore,emerging approaches such as genome editing,high-throughput phenomics,and pan-omics promise to deepen our understanding of tomato stress adaptation and facilitate the development of climate-resilient cultivars.展开更多
基金financially supported by the National Natural Science Foundation of China(32172505,323B2055,32272484)the Natural Science Foundation of Jilin Province,China(20230101156JC)the National Foreign Experts Program,China(G2023129011L)。
摘要Phytopathogenic fungi can weaken the effectiveness of antifungal chemicals from plants and artificial synthesis through a xenobiotic detoxification system.Nevertheless,the transcription factors responsible for transcriptional activation of xenobiotic detoxification genes in phytopathogenic fungi are rarely reported.Here,we show that a GATA transcription factor,SsGATA1,regulates the transcription of drug efflux pump genes,thus contributing to tolerance to various types of chemical fungicides,including propiconazole,caspofungin,and azoxystrobin in Sclerotinia sclerotiorum.Similarly,SsGATA1 also confers tolerance to isothiocyanate and flavonols,two compounds reported as broad-spectrum antifungal chemicals,by mediating the transcription of the isothiocyanate hydrolase SsSaxA.Importantly,SsGATA1 positively regulates pathogenicity,which is attributed to the upregulation of hydrolases and SsSaxA during infection.Furthermore,SsGATA1 is responsible for tolerance to several stresses.Our findings demonstrate that SsGATA1 plays roles in multidrug resistance and pathogenicity by activating the transcription of hydrolases and xenobiotic detoxification genes.
基金supported by the National Eye Institute,grant number R00EY030918the Association for Research in Vision and Ophthalmology(ARVO)Genentech Career Development Award to XCD。
摘要Neuronal cells require precise and stable control of gene expression throughout their extended lifespan,which presents numerous challenges for gene transcription.While traditional studies of transcriptional regulation have primarily focused on canonical DNA-binding factors,there is an increasing recognition of the role of regulatory RNAs and RNA-binding proteins(RBPs)in modulating this process.
基金supported by the National Natural Science Foundation of China(31872706)the National Key Research and Development Program of China(2019 YFD1000603).
摘要Zanthoxylum bungeanum is an economically important crop worldwide due to its high content of aroma-producing monoterpenoids,and development of varieties with enhanced flavor and overall quality is a crucial research area.However,the transcriptional regulatory mechanisms underlying monoterpenoid synthesis in Z.bungeanum remain unclear,hindering these breeding efforts.In this study,RNA sequencing,gas chromatography–mass spectrometry,and other molecular biology techniques were used to identify the underlying transcriptional regulation mechanisms.Two transcription factors,ZbbHLH2 and ZbERF6,were identified as key regulators of monoterpenoid synthesis in Z.bungeanum that upregulate various monoterpenoid synthesis-associated genes and are novel transcriptional activators of ZbIDI,which encodes the rate-limiting enzyme in plant monoterpenoid synthesis.Functional analysis revealed that the expression of three genes[1]modulates monoterpenoid accumulation in Z.bungeanum peel.These findings provide novel insights into the metabolic regulatory network of monoterpenoid synthesis in Z.bungeanum peel,offer potential strategies for the biofortification of specific monoterpenoids,and will promote the development of Z.bungeanum germplasm for targeted breeding and quality improvement.
基金supported by the earmarked fund for China Agriculture Research System(Grant No.CARS-30-Z-16)Natural Science Basic Research Program of Shaanxi(Grant No.2023-JC-QN-0186).
摘要Sugars are crucial in determining fruit quality and significantly affect the commercial value.Sucrose is the primary soluble sugar in ripe peach fruit.However,the regulatorymechanism of sucrose synthesis in peach fruit,especially during natural ripening,remains largely unexplored.This study identified two structural genes of peach(Prunus persica,‘Jinlinghuanglu’),PpSUS1 and PpSPS2,whose expression was strongly correlated with sucrose accumulation.The transcription factors that regulated the expression of these two genes during peach fruit ripening were screened;and three NACs(NAM,ATAF1/2 and CUC2),whose expression also significantly correlated with sucrose accumulation,were identified.Notably,PpNAP4(NAC-like,activated by APETALA3/PISTILLATA)displayed the highest activation activity toward the PpSUS1 and PpSPS2 promoters.The direct binding activity was confirmed using luciferase imaging and electrophoretic mobility shift assays.The sucrose content and expression of sucrose synthesis-related genes significantly increased when PpNAP4 was overexpressed in peach fruit and the tomato nor mutant.Moreover,PpNAP4 functioned synergistically with PpNAP6 to modulate sucrose synthesis,and PpNAP4 targeted its own promoter and feedback-activated its own expression.This research unveils a novel regulatory mechanism controlling sucrose accumulation in peach fruit.
基金supported by the China Agricultural Research System(Grant No.CARS-09)the Central Government Guiding Local Science and Technology Development Project(Grant No.YDZX2023029)the Gansu Planning Projects on Science and Technology(Grant No.23CXNJ0013).
摘要Flavonoids,abundant in the fruits,are pivotal to their growth,development,and storage.In addition,they have significant beneficial effects on human health.Consequently,research is increasingly concentrating on the regulatory mechanisms governing flavonoid biosynthesis in fruits.Phytohormones are involved in the regulation of flavonoid biosynthesis.The abscisic acid,ethylene,jasmonic acid,cytokinins,and brassinosteroids promote flavonoid biosynthesis,while auxin negatively regulates flavonoid biosynthesis.Subsequently,transcription factors from the MYB,bHLH,WRKY,NAC,and bZIP families are pivotal in regulating flavonoid biosynthesis.In addition,non-coding RNAs(microRNA and lncRNA)also participate in the regulation of flavonoids biosynthesis.MicroRNAs are generally believed to negatively regulate flavonoid metabolism in fruits,while lncRNAs have the opposite effect.Furthermore,the interactions between plant hormones,transcription factors,and non-coding RNAs in fruit flavonoid biosynthesis were analyzed.Ultimately,a foundational regulatory network for fruit flavonoid biosynthesis was hereby established.
基金supported by SISSA(intramural funding to AM)International FOXG1 Research Foundation(Grant to AM)+1 种基金Italian Ministery of University and Research(Grant PRIN222022M95RC7 to AM)Fondazione Telethon(Grant GMR22T2018 to AM).
摘要Moving from the most recent results on Foxg1 biology,we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest,involved in controlling both transcription and post-transcriptional steps of gene expression.Then,after further analysis of the literature,we report evidence that,not strictly limited to neurodevelopmental effectors,such pleiotropy also applies to other transcription factors,involved in physiology and homeostasis.Furthermore,through the systematic analysis of a major public protein-protein interaction database,we gather strong evidence that the involvement of“canonical”transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon,characterizing hundreds of effectors.Finally,we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario.
基金supported by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia(Grant No.KFU254713).
摘要Pigment biofortification in rice,particularly through enhanced anthocyanin accumulation,is increasingly recognized in Asia for its potential to improve nutritional quality and antioxidant capacity while addressing regional health challenges.However,the regulatory network underlying anthocyanin biosynthesis in rice remains incompletely characterized,especially regarding MYB transcription factors that may control pigment accumulation in diverse germplasm.In this study,a genome-wide analysis of MYB transcription factors in Oryza sativa subsp.japonica identified 109 OsMYB genes.Phylogenetic comparison with known anthocyanin regulators from Arabidopsis thaliana and Oryza rufipogon revealed conserved clades containing potential pigment-related regulators.Integrative analyses including gene structure,conserved motif identification,promoter cis-element profiling,and miRNA target prediction were conducted to explore their regulatory potential.Expression profiling during grain development in black and mixed rice identified 32 OsMYB genes as potential candidates associated with anthocyanin accumulation.Promoter analysis revealed enrichment of light-responsive,stress-responsive,and developmental regulatory elements,suggesting coordinated regulation by environmental and developmental signals.Predicted interactions with several Osa-miRNAs further indicate potential post-transcriptional control of these genes.Among the candidates,OsMYB65 showed strong differential expression in pigmented rice grains and possessed multiple regulatory elements associated with anthocyanin biosynthesis,highlighting it as a promising regulator.Overall,this integrative genome-wide analysis identifies a prioritized set of MYB transcription factors that may regulate anthocyanin biosynthesis in rice,providing valuable targets for functional validation and pigment-oriented crop improvement.
基金supported by the National Natural Science Foundation of China(32370361 and 32321163646)Guangdong Special Support Program(NYQN2024009)+1 种基金Science and Technology Planning Project of Guangdong Province,China(2021B1212040008)Laboratory of Lingnan Modern Agriculture Project(NG2021002 and NT2025008).
摘要Autophagy is a highly conserved intracellular recycling process in eukaryotes that delivers cellular components to the lysosome or vacuole for degradation,thereby maintaining intracellular homeostasis.Acting as a quality control system,autophagy plays a pivotal role in plant growth,development,and adaptation to environmental challenges.The regulation of autophagy under stress conditions involves multi-layered mechanisms,including transcriptional,epigenetic,and post-translational controls.Transcription factors from families such as WRKY,NO APICAL MERISTEM/ARABIDOPSIS TRANSCRIPTION ACTIVATION FACTOR/CUP-SHAPED COTYLEDON(NAC),and basic leucine zipper(bZIP)directly bind to the promoters of autophagy-related(ATG)genes,thereby integrating stress-responsive signal pathways to orchestrate autophagic activity dynamically.Epigenetic modifications,including histone modifications,DNA methylation,N6-methyladenosine(m6A)methylation,and microRNA-mediated silencing,further fine-tune expression of ATG genes in response to changing environments.At the post-translational level,modifications such as phosphorylation,ubiquitination,acetylation,persulfidation,and S-nitrosylation serve as rapid regulatory switches that modulate autophagosome formation under stress.This review summarizes recent advances in elucidating these regulatory layers,highlighting how these regulators collectively modulate autophagy to improve plant tolerance to environmental cues.Unraveling these mechanisms will expand our understanding of the autophagy regulatory network in plants and provide potential strategies for improving stress tolerance in crops.
基金supported by the National Key Research and Development Program of China to W.Tian (2022YFA1104400)the National Natural Science Foundation of China to T.Chen (82100959)a grant from the Sichuan Science and Technology Program to Z.Liu (2024YFFK0068)。
摘要Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.
基金supported by the National Natural Science Foundation of China(Grant Nos.32402528 and 32372665)。
摘要The HD-ZIP gene family,a group of plant-specific transcription factors,plays pivotal regulatory roles in various aspects of plant growth and development.Accumulating evidence has demonstrated the extensive involvement of HD-ZIP members in regulating reproductive developmental processes.This review systematically summarizes both the structural characteristics of the four HD-ZIP subfamilies(Ⅰ-Ⅳ)and their distinct regulatory roles in plant reproductive development.Recent studies reveal that a conserved HD-ZIPⅠclade serves as a core regulator of key reproductive processes,ranging from spike development in monocots(e.g.,barley Vrs1 and maize GT1)to sex determination in dicots(e.g.,cucumber CmHB40 and persimmon MeGI).Meanwhile,members of other subfamilies(HD-ZIPⅡ-Ⅳ)contribute significantly to diverse reproductive processes including pistil development,floral organ formation,and anther development,among others.This review provides a comprehensive synthesis of HD-ZIP subfamily functions in reproductive development,integrating current knowledge while highlighting critical research gaps.These insights aim to provide theoretical foundations for functional characterization and potential applications of HDZIP reproductive regulators,while advancing our understanding of transcriptional regulation mechanisms in plant reproductive development.
基金supported by the Medjaden Academy&Research Foundation for Young Scientists,No.MJR202510105(to XM)the Doctoral Research Innovation Program of the Jilin Provincial Department of Education,No.JJKH20250213BS(to XM)+3 种基金the Scientific Research Innovation Program for Doctoral Students,Jilin University,No.2024KC137(to XM)the Feihe Research Fund for Constitution,Nutrition,Health,No.CNS-Feihe2020A36(to FZ)the Natural Science Foundation of Qingdao in China,No.23-2-1-204-zyyd-jch(to TG)the National Natural Science Foundation of China,Nos.82273673 and 82073581(both to JL)。
摘要Alzheimer's disease is characterized by hippocampal neuronal apoptosis,which leads to cognitive decline.The pathophysiology of Alzheimer's disease is largely driven by disrupted cellular metabolism and insufficient neuronal energy supply.However,current treatments for Alzheimer's disease remain limited because of side effects and disease complexity.Increasing evidence suggests that amyloid-βoligomer-induced neuronal insulin resistance and metabolic dysfunction play key roles in Alzheimer's disease progression,yet their underlying mechanisms and therapeutic strategies remain unclear.In this translational preclinical study,we combined a case-control analysis,in vitro cell assays,and in vivo experiments using amyloid precursor protein/presenilin 1 transgenic mice to investigate whether transcriptional regulation of key regulatory factors restores neuronal energy supply and improves Alzheimer's disease-induced pathology.The case-control analysis identified pre-B-cell leukemia transcription factor 1 as a crucial regulator of brain metabolic homeostasis in Alzheimer's disease.We developed a blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein to enhance pre-B-cell leukemia transcription factor 1 expression,with the aim of restoring neuronal energy supply and reducing apoptosis.Mechanistic investigations using Alzheimer's disease models revealed that pre-B-cell leukemia transcription factor 1 transcriptionally upregulates insulin receptor substrate 1 by interacting with its promoter,which resulted in augmented insulin signaling.Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 downregulated PDK4,significantly upregulated the expression of pyruvate dehydrogenase,and promoted mitochondrial oxidative phosphorylation activity,which inhibited the abnormally enhanced glycolytic flux,increased adenosine triphosphate production,and ultimately helped restore neuronal energy homeostasis.Therapeutic administration of trans-activator of transcription-pre-B-cell leukemia transcription factor 1 in amyloid precursor protein/presenilin 1 transgenic mice significantly enhanced cognitive performance,diminished hippocampal neuronal apoptosis,and mitigated amyloid-βdeposition.No significant hepatotoxicity,nephrotoxicity,or other detectable adverse effects were observed within the dose ranges and time windows of administration.Taken together,we identified pre-B-cell leukemia transcription factor 1 as a crucial transcriptional regulator of neuronal energy metabolism in Alzheimer's disease.Moreover,we elucidated the molecular mechanism through which the pre-B-cell leukemia transcription factor 1-insulin receptor substrate 1 signaling axis sustains metabolic homeostasis.Furthermore,we demonstrated that the blood-brain barrier-permeable trans-activator of transcription-pre-B-cell leukemia transcription factor 1 fusion protein constitutes a mechanistically innovative and highly translatable therapeutic strategy for Alzheimer's disease.
基金supported by Hebei Natural Science Foundation(H2024206476)Medical Science Research Project of Hebei(20240101).
摘要Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.
基金supported by the Natural Science Foundation of Jiangsu Province(Grant No.BK20200278)China Agriculture Research System(Grant No.CARS-30)+1 种基金Species Conservation Project of Crop Germplasm Resources(Peach and Strawberry)in Jiangsu Province(Grant No.2023-SJ-011)Project of Seed Industry Revitalization in Jiangsu Province(Grant No.JBGS[2021]016).
摘要As the abundant phenolic substance in peach fruit,chlorogenic acid(CGA)has various biological activities and is an important target for improving the nutritional and resistance qualities.Nevertheless,the gene functions and regulatory mechanisms of CGA biosynthesis in peach fruit are poorly understood.Using gene expression patterns from different developmental stages and different peach cultivars,one structural gene PpHCT5 was identified as being involved in CGA biosynthesis.An in vitro enzyme activity assay confirmed that the PpHCT5 protein catalyzed the biosynthesis of caffeoyl CoA and quinic acid into CGA.The in vivo functional validation confirmed that PpHCT5 overexpression increased CGA accumulation in transgenic plants,including peach,tomato,and tobacco.Furthermore,upstream transcription factors of PpHCT5 were identified.PpMYB62 and PpbHLH14 activated PpHCT5 expression by directly binding promoter MBS or G-box elements,thereby inducing CGA accumulation in peach fruit.Additionally,PpMYB308 interactions with PpbHLH14 promoted the activating effect of PpbHLH14 on PpHCT5,thereby positively regulating CGA biosynthesis.Thus,a regulatory network of PpMYB and PpbHLH transcription factors to modulate the PpHCT5-mediated CGA biosynthesis pathway was constructed.It will be useful for elucidating the complex mechanisms underlying CGA biosynthesis and provide a theoretical basis for the development of resistance and increased CGA content breeding in peach.
基金supported by the Foundation Project:National Natural Science.Foundation of China(Nos.:82460249,82100417,81760094)The Foundation of Jiangxi Provincial Department of Science and Technology Outstanding Youth Fund Project(20212BAB206022,20242BAB23080).
摘要Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.
基金supported by the National Natural Science Foundation of China(32372667)。
摘要Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,while little is known about the negative regulators.CRISPR/Cas9 gene-editing technology,with the advantage of precise genetic modification,is a desirable tool for breeding biofortified materials and exploring potential molecular mechanisms.In this study,a transcriptional repressor,Sl MYB32,was characterized in tomato fruit.Phenotype and metabolomic analyses confirmed that knockout of Sl MYB32 resulted in increased accumulation of flavonols and flavanones,especially about 1 mg g-1FW of quercetin 3-O-rutinoside(rutin).Transcriptome analysis indicated that expression of key genes Sl PAL6,Sl4CL3 and Sl4CL4 as well as five candidate Sl UGTs were significantly up-regulated in slmyb32 mutants.Dual-luciferase and EMSA assays indicated Sl MYB32 could bind to and repress promoter activities of Sl PAL6 and Sl4CL3.Expression of 27 transcription factors belonging to 12 families was significantly changed in slmyb32 mutants,among which two Sl MYBs,two Sl NACs,two Sl AP2s and one Sl WRKY were clustered with known flavonoid regulators.Our results provide new insights into improving bioactive compounds in fruit and understanding negative regulatory mechanisms in flavonol and flavanone biosynthesis.
基金supported by the National Natural Science Foundation of China(32372076,32001607)the Fundamental Research Funds for the Central Universities(SWU-XDJH202315)。
摘要Starch is the most abundant accumulated substance in the grains of sorghum(Sorghum bicolor),the 5th most world-widely cultivated cereal crop,and is widely used by humans,especially in the direction of brewing in China.However,there are currently few reports on the starch biosynthesis regulatory mechanism in sorghum grains.Here,we employed RNA-seq and ATAC-seq strategies to discover the transcriptional regulation network responsible for starch biosynthesis in sorghum grains.Our results profiled all mRNAs in the sorghum grains at nine development stages covering the inflorescence,and grains from 3 to 30 days after pollination(DAP).Analysis of the gene sets determined temporal programs of gene expression,including thousands of transcription factor(TF)genes.We found a close correlation between the sequentially expressed gene sets and distinct cellular and metabolic programs of the developing grains.The cis-elements serving as binding sites of multiple TFs were identified via a comparative ATAC-seq assay.Cis-elements capable of binding TFs were also identified within the promoter regions of starch biosynthesis related genes(SBRGs).Moreover,the NAC family TF of SbNAC68 highly expressed in developing grains and demonstrated co-expression patterns with SBRGs.Furthermore,SbNAC68 was confirmed to bind to 5′-ACGCAA-3′,a typical motif of binding site for the TFs from NAC family,to affect the promotor activities of SBRGs and regulate their transcriptions.Collectively,through multiply omics strategies and the case dissection of SbNAC68,the present study provides molecular insights of transcriptional regulations into starch biosynthesis in sorghum grains.
基金supported by Chung Shan Medical University Hospital,Taiwan(Yueh-Chun Lee,grant No.CSH-2021-C-027)by the National Science and Technology Council(Wen-Wei Chang,grant No.114-2320-B-040-005-MY3).
摘要Backgrounds:Triple-negative breast cancer(TNBC)is highly aggressive,insensitive to radiotherapy,and exhibits increased cancer stem cell(CSC)properties,contributing to poor patient outcomes.B-cell lymphoma 2(BCL2)associated transcription factor 1(BCLAF1)is an oncogene in certain cancers,but its role in TNBC is unclear.This study investigated BCLAF1’s involvement in radioresistance and CSC activity in TNBC.Methods:BCLAF1 expression and clinical significance were analyzed using The Cancer Genome Atlas(TCGA)breast cancer dataset.Radioresistant MDA-MB-231 cells were used to examine BCLAF1’s function.Proto-oncogene SRC(SRC)overexpression,BCLAF1 knockdown,dasatinib treatment,and hypoxia inducible factor 1 subunitα(HIF-1α)inhibition were employed to elucidate regulatory mechanisms.CSC activity was assessed using tumorsphere formation assays.Results:Elevated BCLAF1 mRNA levels were associated with advanced pathological and T stages(analysis of variance[ANOVA],p=1.4×10−3)and poorer overall survival by Kaplan–Meier analysis(p=0.021).BCLAF1 expression was positively correlated with SRC signaling pathway-associated genes,including Kirsten rat sarcoma viral oncogene homolog(KRAS),GTPase-activating protein-binding protein 1(G3BP1),and phosphoinositide-3-kinase regulatory subunit 1(PIK3R1).Radioresistant cells exhibited higher BCLAF1 expression.SRC overexpression reduced radiosensitivity,while increasing BCLAF1 levels.BCLAF1 knockdown suppressed tumorsphere formation.Dasatinib decreased BCLAF1,HIF-1α,and stemness proteins,including octamer-binding transcription factor 4(OCT-4),Notch intracellular domain(NICD),and cellular myelocytomatosis oncogene(c-Myc).BCLAF1 knockdown diminished nuclear HIF-1α,and HIF-1αinhibition abrogated BCLAF1-induced tumorsphere formation.Conclusions:BCLAF1 enhances radioresistance and CSC properties in TNBC via SRC-HIF-1αsignaling,suggesting that BCLAF1 is a potential therapeutic target to overcome radioresistance in TNBC.
基金supported by the Yazhouwan Laboratory Grant(2024ZD0408003 to X.G.Z.),STI 2030 Major Project(2023ZD04072 to Q.S.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0630301 to X.G.Z.and XDB0630101 to M.J.L.).
摘要Photosynthesis fuels crop growth and yield,yet the regulatory networks coordinating photosynthetic gene expression with carbon allocation remain incompletely understood.Here,we construct a gene regulatory network(GRN)for rice photosynthesis by integrating time-resolved RNA-seq,ATAC-seq,and promoter cis-element analyses.We identify nine hub transcription factors(TFs),four of which(OsPIL13,OsbZIP72,OsCGA1,and OsGLK1)exhibit strong leaf-specific,light-inducible expression patterns.Overexpression of OsPIL13,OsbZIP72,or OsGLK1 using photosynthetic tissue-specific promoters significantly enhanced the light-saturated photosynthetic rate(Asat)across developmental stages,with OsPIL13 overexpression increasing Asat by up to 57%during grain filling.While several hub TFs boosted photosynthetic capacity,consistent improvements in biomass and grain yield under field conditions were rare.Notably,OsGLK1 overexpression confers stable yield gains across multiple growing seasons.Comparative transcriptomic analysis indicates that OsGLK1 also upregulates genes involved in brassinosteroid biosynthesis and sugar and lipid transporter genes,potentially linking photosynthetic output to growth and resource allocation.Collectively,our findings indicate that enhancing photosynthesis alone is insufficient to guarantee yield improvement;rather,the coordinated regulation of photosynthetic capacity and downstream carbon utilization is essential for sustainable productivity gains in rice.
基金supported by the National Natural Science Foundation of China,China(32372030,32560439)the Applied Basic Research Foundation of Yunnan Province,China(202401BC070005,202501AT070184).
摘要Plant height is critical for crops in agricultural research and practice.Optimizing plant height helps to increase yield and lodging resistance.The green revolution gene semi-dwarf 1(SD1)encoding GA 20-oxidase 2(GA20ox2)has been widely used in modern rice breeding.However,the molecular mechanism of how SD1 is transcriptionally regulated remains elusive.TCP proteins,one family of the plantspecifictranscription factors(TFs),have been proved to widely distribute in plants and play important roles in plant growth and development.Here,we report a TCP TF OsTCP4,which belongs to class I clade TCP,plays critical roles in regulating plant height of rice through acting as a transcriptional repressor of SD1.OsTCP4 is a nuclear-localized TF,which has a preferential transcriptional accumulation in stem nodes and tiller bases.ostcp4 knock-out mutants displayed higher plant height compared with WT,while overexpression of OsTCP4 reduced plant height compared with WT,which was confirmedby two cultivars on four planting sites of Yunnan under three-year investigation.The expression of SD1 was upregulated in ostcp4 mutants and reduced in OsTCP4-overexpression plants.Moreover,OsTCP4 protein directly binds to the promoter region of SD1.The genetic regulation between OsTCP4 and SD1 was further verifiedwith ossd1 tcp4 double mutant.Moreover,distinction of plant height in ostcp4 lines and OsTCP4-OE lines is caused by different concentrations of GA1.Taken together,OsTCP4 acts as a transcriptional repressor of SD1 and it may play a critical role in rice growth and development through the fine-tuningof GA1 biosynthesis.
基金supported by the National Natural Science Foundation of China(Grant No.32472743)the National Key R&D Program of China(Grant No.2022YFE0100900)the Earmarked Fund for China Agricultural Research System(Grant No.CARS-23-A13)。
摘要Tomato(Solanum lycopersicum),one of the world's most economically and nutritionally important crops,faces increasing challenges from abiotic stresses such as drought,salinity,and temperature extremes,which are being exacerbated by climate change.Understanding the molecular mechanisms underlying tomato's adaptation to these environmental constraints is essential for identifying stress-resilient genes and achieving sustainable production.This review synthesizes recent progress in elucidating the transcriptional and signaling responses of tomato to major abiotic stresses.Such stresses induce a series of physiological disorders,including osmotic imbalance,membrane damage,photosynthetic inhibition,and oxidative stress.Complex signal transduction networks mediate the perception and response to these stresses,involving second messengers,diverse protein kinases,and multiple phytohormones.These signaling pathways converge to orchestrate transcriptional reprogramming through the coordinated activity of various transcription factors,which modulate downstream genes to enhance antioxidant defense,osmotic adjustment,and ion homeostasis.Despite significant progress,substantial knowledge gaps remain regarding signal cross-talk and the integration of responses under compound stresses.Advances in multi-omics technologies are accelerating the identification of key stress-responsive genes,proteins,and metabolites,offering new opportunities for molecular breeding.Furthermore,emerging approaches such as genome editing,high-throughput phenomics,and pan-omics promise to deepen our understanding of tomato stress adaptation and facilitate the development of climate-resilient cultivars.