Genome-wide definition of regulatory elements in hematopoietic stem cell differentiation
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ABSTRACT:
PROVIDER: PRJNA289504 | ENA |
REPOSITORIES: ENA
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Project description:The rapidly expanding information on the structural and functional characteristics of the human genome allows the development of genome-wide approaches to investigate the molecular circuitry wiring the genetic and epigenetic programs of clinically relevant stem/progenitor cells. Here, we define the transcriptional and epigenetic profile of human hematopoietic stem/progenitor cells (HSPC) and their committed, early myeloid and erythroid progeny. Cap Analysis of Gene Expression showed that the transcriptional state is largely maintained in the transition from early hematopoietic stem/progenitors to committed progenitor/precursors. A large fraction of differentially expressed active promoters in each cell type were classified as novel, possibly driving the expression of transcripts involved in HSPC commitment. Unannotated promoters harbored an enhancer chromatin signature, were enriched in cell-specific transcription factor binding sites, and were close to protein-coding cell-specific genes. To obtain a genome-wide description of regulatory regions, we performed ChIP-seq for histone modifications typical of promoters, enhancers and super-enhancers. ChIP-defined promoters were shared by HSPC and committed cells, whereas enhancer usage consistently changed upon commitment, thus indicating that the fine regulation of commitment is carried out by enhancer elements. The expression level of genes targeted by enhancers and super-enhancers was moderately higher in cells actively using these regulatory elements. However, functional annotation of targeted genes showed a low enrichment for cell-specific gene ontology categories. Finally, we used Moloney leukemia virus (MLV) to map functional regions of chromatin. Genomic regions targeted by MLV co-mapped with a fraction of epigenetically defined active regulatory elements, with two-third of MLV integrations falling in enhancers, and one-third in promoters. Most of MLV-targeted regulatory regions were differentially used between HSPC and their committed progeny. Analysis of the expression levels of promoters close to cell-specific MLV-targeted enhancers and functional assays indicated that MLV-defined regulatory regions are bona fide cell-specific enhancers. Finally, gene ontology analyses showed that MLV-targeted genes related to the peculiar cell identity. Overall, this study provided an overview of the differential transcriptional and epigenetic programs of HSPC and committed progenitors and represents a unique source of regulatory regions involved in HSPC commitment.
2016-04-20 | GSE64888 | GEO
Project description:The rapidly expanding information on the structural and functional characteristics of the human genome allows the development of genome-wide approaches to investigate the molecular circuitry wiring the genetic and epigenetic programs of clinically relevant stem/progenitor cells. Here, we define the transcriptional and epigenetic profile of human hematopoietic stem/progenitor cells (HSPC) and their committed, early myeloid and erythroid progeny. Cap Analysis of Gene Expression showed that the transcriptional state is largely maintained in the transition from early hematopoietic stem/progenitors to committed progenitor/precursors. A large fraction of differentially expressed active promoters in each cell type were classified as novel, possibly driving the expression of transcripts involved in HSPC commitment. Unannotated promoters harbored an enhancer chromatin signature, were enriched in cell-specific transcription factor binding sites, and were close to protein-coding cell-specific genes. To obtain a genome-wide description of regulatory regions, we performed ChIP-seq for histone modifications typical of promoters, enhancers and super-enhancers. ChIP-defined promoters were shared by HSPC and committed cells, whereas enhancer usage consistently changed upon commitment, thus indicating that the fine regulation of commitment is carried out by enhancer elements. The expression level of genes targeted by enhancers and super-enhancers was moderately higher in cells actively using these regulatory elements. However, functional annotation of targeted genes showed a low enrichment for cell-specific gene ontology categories. Finally, we used Moloney leukemia virus (MLV) to map functional regions of chromatin. Genomic regions targeted by MLV co-mapped with a fraction of epigenetically defined active regulatory elements, with two-third of MLV integrations falling in enhancers, and one-third in promoters. Most of MLV-targeted regulatory regions were differentially used between HSPC and their committed progeny. Analysis of the expression levels of promoters close to cell-specific MLV-targeted enhancers and functional assays indicated that MLV-defined regulatory regions are bona fide cell-specific enhancers. Finally, gene ontology analyses showed that MLV-targeted genes related to the peculiar cell identity. Overall, this study provided an overview of the differential transcriptional and epigenetic programs of HSPC and committed progenitors and represents a unique source of regulatory regions involved in HSPC commitment.
2016-04-20 | GSE70675 | GEO
Project description:The rapidly expanding information on the structural and functional characteristics of the human genome allows the development of genome-wide approaches to investigate the molecular circuitry wiring the genetic and epigenetic programs of clinically relevant stem/progenitor cells. Here, we define the transcriptional and epigenetic profile of human hematopoietic stem/progenitor cells (HSPC) and their committed, early myeloid and erythroid progeny. Cap Analysis of Gene Expression showed that the transcriptional state is largely maintained in the transition from early hematopoietic stem/progenitors to committed progenitor/precursors. A large fraction of differentially expressed active promoters in each cell type were classified as novel, possibly driving the expression of transcripts involved in HSPC commitment. Unannotated promoters harbored an enhancer chromatin signature, were enriched in cell-specific transcription factor binding sites, and were close to protein-coding cell-specific genes. To obtain a genome-wide description of regulatory regions, we performed ChIP-seq for histone modifications typical of promoters, enhancers and super-enhancers. ChIP-defined promoters were shared by HSPC and committed cells, whereas enhancer usage consistently changed upon commitment, thus indicating that the fine regulation of commitment is carried out by enhancer elements. The expression level of genes targeted by enhancers and super-enhancers was moderately higher in cells actively using these regulatory elements. However, functional annotation of targeted genes showed a low enrichment for cell-specific gene ontology categories. Finally, we used Moloney leukemia virus (MLV) to map functional regions of chromatin. Genomic regions targeted by MLV co-mapped with a fraction of epigenetically defined active regulatory elements, with two-third of MLV integrations falling in enhancers, and one-third in promoters. Most of MLV-targeted regulatory regions were differentially used between HSPC and their committed progeny. Analysis of the expression levels of promoters close to cell-specific MLV-targeted enhancers and functional assays indicated that MLV-defined regulatory regions are bona fide cell-specific enhancers. Finally, gene ontology analyses showed that MLV-targeted genes related to the peculiar cell identity. Overall, this study provided an overview of the differential transcriptional and epigenetic programs of HSPC and committed progenitors and represents a unique source of regulatory regions involved in HSPC commitment.
2016-04-20 | GSE70674 | GEO
Project description:The rapidly expanding information on the structural and functional characteristics of the human genome allows the development of genome-wide approaches to investigate the molecular circuitry wiring the genetic and epigenetic programs of clinically relevant stem/progenitor cells. Here, we define the transcriptional and epigenetic profile of human hematopoietic stem/progenitor cells (HSPC) and their committed, early myeloid and erythroid progeny. Cap Analysis of Gene Expression showed that the transcriptional state is largely maintained in the transition from early hematopoietic stem/progenitors to committed progenitor/precursors. A large fraction of differentially expressed active promoters in each cell type were classified as novel, possibly driving the expression of transcripts involved in HSPC commitment. Unannotated promoters harbored an enhancer chromatin signature, were enriched in cell-specific transcription factor binding sites, and were close to protein-coding cell-specific genes. To obtain a genome-wide description of regulatory regions, we performed ChIP-seq for histone modifications typical of promoters, enhancers and super-enhancers. ChIP-defined promoters were shared by HSPC and committed cells, whereas enhancer usage consistently changed upon commitment, thus indicating that the fine regulation of commitment is carried out by enhancer elements. The expression level of genes targeted by enhancers and super-enhancers was moderately higher in cells actively using these regulatory elements. However, functional annotation of targeted genes showed a low enrichment for cell-specific gene ontology categories. Finally, we used Moloney leukemia virus (MLV) to map functional regions of chromatin. Genomic regions targeted by MLV co-mapped with a fraction of epigenetically defined active regulatory elements, with two-third of MLV integrations falling in enhancers, and one-third in promoters. Most of MLV-targeted regulatory regions were differentially used between HSPC and their committed progeny. Analysis of the expression levels of promoters close to cell-specific MLV-targeted enhancers and functional assays indicated that MLV-defined regulatory regions are bona fide cell-specific enhancers. Finally, gene ontology analyses showed that MLV-targeted genes related to the peculiar cell identity. Overall, this study provided an overview of the differential transcriptional and epigenetic programs of HSPC and committed progenitors and represents a unique source of regulatory regions involved in HSPC commitment.
2016-04-20 | GSE70676 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
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Project description:Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
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Project description:Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
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Project description:Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
2022-12-09 | GSE198773 | GEO
Project description:Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. Multiple genome-wide studies have mapped chromatin and genomic features of such elements. However, the enhancer definition is operational, and no global experiments have been conducted to date that identify their cell type and cell stage-specific transcription stimulatory activity in a chromatin context. Here, we describe a high-throughput method that identifies thousands of cis-elements capable of stimulating transcriptional activity from a minimal promoter using the blood progenitor differentiation from embryonic stem cells as model. We show that hematopoietic specification and blood cell-specific gene expression are controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work presents a major advance in our understanding of developmental gene expression control in the hematopoietic system and beyond.
2022-12-09 | GSE198774 | GEO