WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previo...WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previous studies have identified hundreds of WRKY TFs in peanut.However,their functions and regulatory networks remain unclear.Simultaneously,the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF,which has a homoeologous relationship with AhTWRKY106 TF in A.hypogaea cv.Tifrunner.To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes,DNA affinity purification sequencing(DAP-seq)was performed to detect the binding sites of TFs at the genome-wide level.A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs.The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs.A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process.In addition,RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress.The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes,and they nearly equal the numbers of downstream genes from the two A.hypogaea cv.Tifrunner subgenomes.These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.展开更多
Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic ...Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance.The NAC proteins are crucial and plant-specific transcription factors(TFs)that are involved in cotton growth,development,and stress responses.The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible.Based on cotton genomic data,genome-wide identification and analyses have revealed potential functions of cotton NAC genes.Here,we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought,salt,and Verticillium wilt-related stresses,as well as leaf senescence and the development of fibers,xylem,and glands.The detailed regulatory network of NAC proteins in cotton is also elucidated.Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation,participate in several biological processes by interacting with related proteins,and regulate the expression of downstream genes.Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance.This review elucidates the latest findings on the functions and regulation of cotton NAC proteins,broadens our understanding of cotton NAC TFs,and lays a fundamental foundation for further molecular breeding research in cotton.展开更多
Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thali...Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thaliana.This mechanistically challenging process results from multiple inputs including gene interactions,cellular geometry,growth rates,and coordinated cell divisions.To better understand how this complex genetic and cellular information controls leaf growth,we developed a mathematical model of flat leaf production.This two-dimensional model describes the gene interactions in a vertex network of cells which grow and divide according to physical forces and genetic information.Interestingly,the model predicts the presence of an unknown additional factor required for the formation of biologically realistic gene expression domains and iterative cell division.This two-dimensional model will form the basis for future studies into robustness of adaxial-abaxial patterning.展开更多
Plant oils play a crucial role in human nutrition,industrial applications and biofuel production.While the enzymes involved in fatty acid(FA)biosynthesis are well-studied,the regulatory networks governing these proces...Plant oils play a crucial role in human nutrition,industrial applications and biofuel production.While the enzymes involved in fatty acid(FA)biosynthesis are well-studied,the regulatory networks governing these processes remain largely unexplored.This review explores the intricate regulatory networks modulating seed oil biosynthesis,focusing on key pathways and factors.Seed oil content is determined by the efficiency of de novo FA synthesis as well as influenced by sugar transport,lipid metabolism,FA synthesis inhibitors and fine-tuning mechanisms.At the center of this regulatory network is WRINKLED1(WRI1),which plays a conserved role in promoting seed oil content across various plant species.WRI1 interacts with multiple proteins,and its expression level is regulated by upstream regulators,including members of the LAFL network.Beyond the LAFL network,we also discuss a potential nuclear factor-Y(NF-Y)regulatory network in soybean with an emphasis on NF-YA and NF-YB and their associated proteins.This NF-Y network represents a promising avenue for future efforts aimed at enhancing oil accumulation and improving stress tolerance in soybean.Additionally,the application of omics-based approaches is of great significance.Advances in omics technologies have greatly facilitated the identification of gene resources,opening new opportunities for genetic improvement.Importantly,several transcription factors involved in oil biosynthesis also participate in stress responses,highlighting a potential link between the two processes.This comprehensive review elucidates the complex mechanisms underlying the regulation of oil biosynthesis,offering insights into potential biotechnological strategies for improving oil production and stress tolerance in oil crops.展开更多
Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain...Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain poorly understood.Here,we present a comprehensive multi-omics atlas of leaves and roots in Ae.speltoides,encompassing transcriptome,DNA methylation,histone modifications,and small RNA profiling.Divergent DNA methylation levels were detected between leaves and roots,and were associated with differences in accumulated 24-nt siRNAs.DNA methylation changes in promoters and gene bodies showed strong connections with altered expression between leaves and roots.Transcriptional regulatory networks(TRN)reconstructed between leaves and roots were driven by tissue-specific TF families.DNA methylation and histone modification act together as switches that shape root and leaf morphogenesis by modulating the binding of tissue-specific TFs to their target genes.The TRNs in leaves and roots reshaped during wheat polyploidization were associated with alterations in epigenetic modi-fications.Collectively,these results not only shed light on the critical contribution of epigenetic regulation in the morphogenesis of leaves and roots in Ae.speltoides but also provide new insights for future investigations into the complex interplay of genetic and epigenetic factors in the developmental biology of common wheat.展开更多
During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial struc...During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.展开更多
Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammal...Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammalian transcriptional regulation andanalyzing the relative benefits of related computational methodologies. One dataset available forsuch an analysis involved gene expression profiling of the early growth factor response to plateletderived growth factor (PDGF) in a human glioblastoma cell line; this study differentiated geneswhose expression was regulated by signaling through the phosphoinositide-3-kinase (PI3K) versus theextracellular-signal regulated kinase (ERK) pathways. We have compared the inferred transcriptionfactors from this previous study with additional predictions of regulatory transcription factorsusing two alternative promoter sequence analysis techniques. This comparative analysis, in which thealgorithms predict overlapping, although not identical, sets of factors, argues for meticulousbenchmarking of promoter sequence analysis methods to determine the positive and negative attributesthat contribute to their varying results. Finally, we inferred transcriptional regulatory networksderiving from various signaling pathways using the CARRIE program suite. These networks not onlyincluded previously described transcriptional features of the response to growth signals, but alsopredicted new regulatory features for the propagation and modulation of the growth signal.展开更多
Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the conce...Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network （TRN） for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model. While many large-scale TRN reconstructions have been reported for yeast, these reconstructions still need to be improved regarding the functionality and dynamic property of the regulatory interactions. In addition, mathematical modeling approaches need to be further developed to efficiently integrate transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner.展开更多
Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly ...Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly understood.Here,we used laser capture microdissection of stem xylem cells coupled with full transcriptome RNA-sequencing to analyze TW formation in Populus trichocarpa.After tree bending,PtrLBD39 was the most significantly induced transcription factor gene;it has a phylogenetically paired homolog,PtrLBD22.CRISPR-based knockout of PtrLBD39/22 severely inhibited TW formation,reducing cellulose and increasing lignin content.Transcriptomic analyses of CRISPR-based PtrLBD39/22 double mutants showed that these two genes regulate a set of TW-related genes.Chromatin immunoprecipitation sequencing(ChIP-seq)was used to identify direct targets of PtrLBD39.We integrated transcriptomic analyses and ChIP-seq assays to construct a transcriptional regulatory network(TRN)mediated by PtrLBD39.In this TRN,PtrLBD39 directly regulates 26 novel TW-responsive transcription factor genes.Our work suggests that PtrLBD39 and PtrLBD22 specifically control TW formation by mediating a TW-specific TRN in Populus.展开更多
Transcriptional regulation,determined by the chromatin structure and regulatory elements interacting at pro-moter regions,is a key step in plant responses to environmental cues.Nitrate(NO3-)is a nutrient signal that r...Transcriptional regulation,determined by the chromatin structure and regulatory elements interacting at pro-moter regions,is a key step in plant responses to environmental cues.Nitrate(NO3-)is a nutrient signal that regulates the expression of hundreds of genes in Arabidopsis thaliana.Here,we integrate mRNA sequencing,genome-wide RNA polymeraseⅡ(RNPⅡ),chromatin immunoprecipitation sequencing,and DNase Sequencing datasets to establish the relationship between RNPⅡoccupancy and chromatin accessibility in response to NO3-treatments in Arabidopsis roots.Genomic footprinting allowed us to identify in vivo regula-tory elements controlling gene expression in response to NO3-treatments.NO3--modulated transcription factor(TF)footprints are important for a rapid increase in RNPⅡoccupancy and transcript accumulation over time.We mapped key TF regulatory interactions and functionally validated the role of NAP,an NAC-domain containing TF,as a new regulatory factor in NO3-transport.Taken together,our study provides a comprehensive view of transcriptional networks in response to a nutrient signal in Arabidopsis roots.展开更多
Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Her...Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.展开更多
Human hematopoiesis starts at early yolk sac and undergoes site-and stage-specific changes over development.The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood.Here,...Human hematopoiesis starts at early yolk sac and undergoes site-and stage-specific changes over development.The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood.Here,we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells(HSPCs)at different developmental stages,including yolk-sac(YS),AGM,fetal liver(FL),umbilical cord blood(UCB)and adult peripheral blood(PB)mobilized HSPCs.These stage-specific HSPCs display differential intrinsic properties,such as metabolism,self-renewal,differentiating potentialities etc.We then generated highly co-related gene regulatory network(GRNs)modules underlying the differential HSC key properties.Particularly,we identified GRNs and key regulators control-ling lymphoid potentiality,self-renewal as well as aerobic respiration in human HSCs.Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells.Therefore,GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.展开更多
Plants are sessile organisms that evolve with a flexible signal transduction system in order to rapidly respond to environmental changes.Drought,a common abiotic stress,affects multiple plant developmental processes e...Plants are sessile organisms that evolve with a flexible signal transduction system in order to rapidly respond to environmental changes.Drought,a common abiotic stress,affects multiple plant developmental processes especially growth.In response to drought stress,an intricate hierarchical regulatory network is established in plant to survive from the extreme environment.The transcriptional regulation carried out by transcription factors(TFs)is the most important step for the establishment of the network.In this review,we summarized almost all the TFs that have been reported to participate in drought tolerance(DT)in plant.Totally 466 TFs from 86 plant species that mostly belong to 11 families are collected here.This demonstrates that TFs in these 11 families are the main transcriptional regulators of plant DT.The regulatory network is built by direct protein-protein interaction or mutual regulation of TFs.TFs receive upstream signals possibly via post-transcriptional regulation and output signals to downstream targets via direct binding to their promoters to regulate gene expression.展开更多
基金funded by the Start-up Foundation for High Talents of Qingdao Agricultural University(No.665/1120012)the Natural Science Foundation of Shandong Province,China(ZR2019QC017)+4 种基金the National Key Research and Development Program,China(2022YFD2300101-1)the Key Research and Development Program of Shandong Province,China(2021LZGC003 and 2021LZGC026-03)Peanut Seed Industry Project in Shandong Province,China(2022LZGC007)the Science&Technology Specific Projects in Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta,China(2022SZX18)the Graduate Student Innovation Program of Qingdao Agricultural University(QNYCX23001).
文摘WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previous studies have identified hundreds of WRKY TFs in peanut.However,their functions and regulatory networks remain unclear.Simultaneously,the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF,which has a homoeologous relationship with AhTWRKY106 TF in A.hypogaea cv.Tifrunner.To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes,DNA affinity purification sequencing(DAP-seq)was performed to detect the binding sites of TFs at the genome-wide level.A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs.The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs.A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process.In addition,RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress.The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes,and they nearly equal the numbers of downstream genes from the two A.hypogaea cv.Tifrunner subgenomes.These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.
基金supported by the Young Scientists Fund of the National Natural Science Foundation of China(32101797)Central Public-interest Scientific Institution Basal Research Fund(No.1610162023020)。
文摘Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance.The NAC proteins are crucial and plant-specific transcription factors(TFs)that are involved in cotton growth,development,and stress responses.The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible.Based on cotton genomic data,genome-wide identification and analyses have revealed potential functions of cotton NAC genes.Here,we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought,salt,and Verticillium wilt-related stresses,as well as leaf senescence and the development of fibers,xylem,and glands.The detailed regulatory network of NAC proteins in cotton is also elucidated.Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation,participate in several biological processes by interacting with related proteins,and regulate the expression of downstream genes.Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance.This review elucidates the latest findings on the functions and regulation of cotton NAC proteins,broadens our understanding of cotton NAC TFs,and lays a fundamental foundation for further molecular breeding research in cotton.
基金supported by the NSF#2039489 to A.Y.H and the NSF#1813071 to C.-S.C.
文摘Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thaliana.This mechanistically challenging process results from multiple inputs including gene interactions,cellular geometry,growth rates,and coordinated cell divisions.To better understand how this complex genetic and cellular information controls leaf growth,we developed a mathematical model of flat leaf production.This two-dimensional model describes the gene interactions in a vertex network of cells which grow and divide according to physical forces and genetic information.Interestingly,the model predicts the presence of an unknown additional factor required for the formation of biologically realistic gene expression domains and iterative cell division.This two-dimensional model will form the basis for future studies into robustness of adaxial-abaxial patterning.
基金supported by Biological Breeding-National Science and Technology Major Project(2024ZD04078)National Natural Science Foundation of China(32090062 and 32090063)+1 种基金National key R&D program of China(2021YFF1001201,2023YFD1200602,and 2021YFF1000104)Chinese Academy of Science leading project(XDA24010105)。
文摘Plant oils play a crucial role in human nutrition,industrial applications and biofuel production.While the enzymes involved in fatty acid(FA)biosynthesis are well-studied,the regulatory networks governing these processes remain largely unexplored.This review explores the intricate regulatory networks modulating seed oil biosynthesis,focusing on key pathways and factors.Seed oil content is determined by the efficiency of de novo FA synthesis as well as influenced by sugar transport,lipid metabolism,FA synthesis inhibitors and fine-tuning mechanisms.At the center of this regulatory network is WRINKLED1(WRI1),which plays a conserved role in promoting seed oil content across various plant species.WRI1 interacts with multiple proteins,and its expression level is regulated by upstream regulators,including members of the LAFL network.Beyond the LAFL network,we also discuss a potential nuclear factor-Y(NF-Y)regulatory network in soybean with an emphasis on NF-YA and NF-YB and their associated proteins.This NF-Y network represents a promising avenue for future efforts aimed at enhancing oil accumulation and improving stress tolerance in soybean.Additionally,the application of omics-based approaches is of great significance.Advances in omics technologies have greatly facilitated the identification of gene resources,opening new opportunities for genetic improvement.Importantly,several transcription factors involved in oil biosynthesis also participate in stress responses,highlighting a potential link between the two processes.This comprehensive review elucidates the complex mechanisms underlying the regulation of oil biosynthesis,offering insights into potential biotechnological strategies for improving oil production and stress tolerance in oil crops.
基金supported by the National Key Research and Development Program of China(2023YFD1200403).
文摘Aegilops speltoides,the closest ancestor of the wheat B subgenome,has been well studied genomically.However,the epigenetic landscape of Ae.speltoides and the effects of epigenetics on its growth and development remain poorly understood.Here,we present a comprehensive multi-omics atlas of leaves and roots in Ae.speltoides,encompassing transcriptome,DNA methylation,histone modifications,and small RNA profiling.Divergent DNA methylation levels were detected between leaves and roots,and were associated with differences in accumulated 24-nt siRNAs.DNA methylation changes in promoters and gene bodies showed strong connections with altered expression between leaves and roots.Transcriptional regulatory networks(TRN)reconstructed between leaves and roots were driven by tissue-specific TF families.DNA methylation and histone modification act together as switches that shape root and leaf morphogenesis by modulating the binding of tissue-specific TFs to their target genes.The TRNs in leaves and roots reshaped during wheat polyploidization were associated with alterations in epigenetic modi-fications.Collectively,these results not only shed light on the critical contribution of epigenetic regulation in the morphogenesis of leaves and roots in Ae.speltoides but also provide new insights for future investigations into the complex interplay of genetic and epigenetic factors in the developmental biology of common wheat.
基金supported by the National Natural Science Foundation of China(82071096 to X.W,31970585,32170544,and 31801056 to Q.B.)the National Key Research and Development Program of China(2017YFC1001800 to X.W.,2018YFC1004703 to Q.B),the Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ179 to J.S.)+1 种基金the Innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20211700)the SHIPM-pi fund No.JY201803 from Shanghai Institute of Precision Medicine,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.
文摘During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.
文摘Determining how cells regulate their transcriptional response toextracellular signals is key to the understanding of complex eukaryotic systems. This study wasinitiated with the goals of furthering the study of mammalian transcriptional regulation andanalyzing the relative benefits of related computational methodologies. One dataset available forsuch an analysis involved gene expression profiling of the early growth factor response to plateletderived growth factor (PDGF) in a human glioblastoma cell line; this study differentiated geneswhose expression was regulated by signaling through the phosphoinositide-3-kinase (PI3K) versus theextracellular-signal regulated kinase (ERK) pathways. We have compared the inferred transcriptionfactors from this previous study with additional predictions of regulatory transcription factorsusing two alternative promoter sequence analysis techniques. This comparative analysis, in which thealgorithms predict overlapping, although not identical, sets of factors, argues for meticulousbenchmarking of promoter sequence analysis methods to determine the positive and negative attributesthat contribute to their varying results. Finally, we inferred transcriptional regulatory networksderiving from various signaling pathways using the CARRIE program suite. These networks not onlyincluded previously described transcriptional features of the response to growth signals, but alsopredicted new regulatory features for the propagation and modulation of the growth signal.
文摘Metabolism is regulated at multiple levels in response to the changes of internal or external conditions. Transcriptional regulation plays an important role in regulating many metabolic reactions by altering the concentrations of metabolic enzymes. Thus, integration of the transcriptional regulatory information is necessary to improve the accuracy and predictive ability of metabolic models. Here we review the strategies for the reconstruction of a transcriptional regulatory network （TRN） for yeast and the integration of such a reconstruction into a flux balance analysis-based metabolic model. While many large-scale TRN reconstructions have been reported for yeast, these reconstructions still need to be improved regarding the functionality and dynamic property of the regulatory interactions. In addition, mathematical modeling approaches need to be further developed to efficiently integrate transcriptional regulatory interactions to genome-scale metabolic models in a quantitative manner.
基金This work was supported by the National Key Research and Development Program of China(no.2016YFD0600106)We also acknowledge financial support from the National Natural Science Foundation of China(grant nos.32001332 and 32001331)+1 种基金the Fundamental Research Funds for the Central Universities of China(grant nos.2572018CL01 and 2572018CL02)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team).
文摘Tension wood(TW)is a specialized xylem tissue formed in angiosperm trees under gravitational stimulus or mechanical stresses(e.g.,bending).The genetic regulation that underlies this important mechanism remains poorly understood.Here,we used laser capture microdissection of stem xylem cells coupled with full transcriptome RNA-sequencing to analyze TW formation in Populus trichocarpa.After tree bending,PtrLBD39 was the most significantly induced transcription factor gene;it has a phylogenetically paired homolog,PtrLBD22.CRISPR-based knockout of PtrLBD39/22 severely inhibited TW formation,reducing cellulose and increasing lignin content.Transcriptomic analyses of CRISPR-based PtrLBD39/22 double mutants showed that these two genes regulate a set of TW-related genes.Chromatin immunoprecipitation sequencing(ChIP-seq)was used to identify direct targets of PtrLBD39.We integrated transcriptomic analyses and ChIP-seq assays to construct a transcriptional regulatory network(TRN)mediated by PtrLBD39.In this TRN,PtrLBD39 directly regulates 26 novel TW-responsive transcription factor genes.Our work suggests that PtrLBD39 and PtrLBD22 specifically control TW formation by mediating a TW-specific TRN in Populus.
基金This work is funded by Institute Milenio iBio-Iniciativa Cientifica Milenio MINECON,Chileby grants from the Fondo de Desarrollo de Areas Prioritarias(FONDAP)Center for Genome Regulation(15090007),Chile+2 种基金Fondo Nacional de Desarrollo Cientifico y Tecnologico(FONDECYT)(1180759),Chileto R.A.G.J.M.A.is supported by postdoctoral grant FONDECYT(3140336),Chile.J.J.is funded by grant MCB-1412948 from the National Science Foundation,United Statesand J.M.by funding from the Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA),Spain(RTA2015-00014-c02-01).We also want to acknowledge the"Severo Ochoa Program for Centers of Excellence in R&DM from the Agenda Estatal de Investigacion of Spain(SEV-2016-0672(2017-2021))for supporting the scientific services used in this work.
文摘Transcriptional regulation,determined by the chromatin structure and regulatory elements interacting at pro-moter regions,is a key step in plant responses to environmental cues.Nitrate(NO3-)is a nutrient signal that regulates the expression of hundreds of genes in Arabidopsis thaliana.Here,we integrate mRNA sequencing,genome-wide RNA polymeraseⅡ(RNPⅡ),chromatin immunoprecipitation sequencing,and DNase Sequencing datasets to establish the relationship between RNPⅡoccupancy and chromatin accessibility in response to NO3-treatments in Arabidopsis roots.Genomic footprinting allowed us to identify in vivo regula-tory elements controlling gene expression in response to NO3-treatments.NO3--modulated transcription factor(TF)footprints are important for a rapid increase in RNPⅡoccupancy and transcript accumulation over time.We mapped key TF regulatory interactions and functionally validated the role of NAP,an NAC-domain containing TF,as a new regulatory factor in NO3-transport.Taken together,our study provides a comprehensive view of transcriptional networks in response to a nutrient signal in Arabidopsis roots.
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0107804)the National Natural Science Foundation of China(81900117,82131430173)the CAMS Initiative for Innovative Medicine(2021-I2M-1–040).
文摘Highly heterogeneous acute myeloid leukemia(AML)exhibits dysregulated transcriptional programs.Transcription factor(TF)regulatory networks underlying AML subtypes have not been elucidated at single-cell resolution.Here,we comprehensively mapped malignancy-related TFs activated in different AML subtypes by analyzing single-cell RNA sequencing data from AMLs and healthy donors.We first identified six modules of regulatory networks which were prevalently dysregulated in all AML patients.AML subtypes featured with different malignant cellular composition possessed subtype-specific regulatory TFs associated with differentiation suppression or immune modulation.At last,we validated that ERF was crucial for the development of hematopoietic stem/progenitor cells by performing loss-and gain-of-function experiments in zebrafish embryos.Collectively,our work thoroughly documents an abnormal spectrum of transcriptional regulatory networks in AML and reveals subtype-specific dysregulation basis,which provides a prospective view to AML pathogenesis and potential targets for both diagnosis and therapy.
基金National Key Research and Development Program of China,Stem Cell and Translational Research(2022YFA1105001)Research Funds from Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR,P.R.China+8 种基金National Natural Science Foundation of China(31971374,32171451)Science and Technology Planning Project of Guangdong Province,China(2023B1212060050,2023B1212120009)Youth Innovation Promotion Association of the Chinese Academy of Sciences(to Y.Z.2023373)China Postdoctoral Science Foundation Funded Project(2023M733516)Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation(ZXXM202201)Guangzhou Key Research and Development Program(202206010041)Guangzhou Science and Technology Program General project(2024A04J3801)Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine(2020B1212060052)Guangdong Province Special Program for Outstanding Talents(to G.P.,2019JC05Y463).
文摘Human hematopoiesis starts at early yolk sac and undergoes site-and stage-specific changes over development.The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood.Here,we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells(HSPCs)at different developmental stages,including yolk-sac(YS),AGM,fetal liver(FL),umbilical cord blood(UCB)and adult peripheral blood(PB)mobilized HSPCs.These stage-specific HSPCs display differential intrinsic properties,such as metabolism,self-renewal,differentiating potentialities etc.We then generated highly co-related gene regulatory network(GRNs)modules underlying the differential HSC key properties.Particularly,we identified GRNs and key regulators control-ling lymphoid potentiality,self-renewal as well as aerobic respiration in human HSCs.Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells.Therefore,GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.
基金supported by Research Initiation Fund for High-level Talents of China Three Gorges University.
文摘Plants are sessile organisms that evolve with a flexible signal transduction system in order to rapidly respond to environmental changes.Drought,a common abiotic stress,affects multiple plant developmental processes especially growth.In response to drought stress,an intricate hierarchical regulatory network is established in plant to survive from the extreme environment.The transcriptional regulation carried out by transcription factors(TFs)is the most important step for the establishment of the network.In this review,we summarized almost all the TFs that have been reported to participate in drought tolerance(DT)in plant.Totally 466 TFs from 86 plant species that mostly belong to 11 families are collected here.This demonstrates that TFs in these 11 families are the main transcriptional regulators of plant DT.The regulatory network is built by direct protein-protein interaction or mutual regulation of TFs.TFs receive upstream signals possibly via post-transcriptional regulation and output signals to downstream targets via direct binding to their promoters to regulate gene expression.
