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Comparative profiling of chromatin state maps and transcription factor occupancy during human fetal and adult erythropoiesis

ABSTRACT: We report the comparative investigation of genome-wide chromatin state maps, transcription factor (TF) occupancy, and gene expression profiles from developing red cell precursors at two developmental stages. Contrasting the similarities and differences between fetal and adult erythropoiesis provides important insights into the erythroid gene expression programs and gene regulatory networks. Specifically, comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that master regulators, such as GATA1 and TAL1, cooperatively act within active enhancers but have little predictive value for stage-specific enhancer activity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of adult-stage expression program. Thus, the combinatorial assembly of master regulators and transcriptional co-regulators at developmental stage-specific enhancers controls gene expression programs and temporal regulation of transcriptional networks in a mammalian genome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE36985 | GEO | 2012/10/05

SECONDARY ACCESSION(S): PRJNA157469

REPOSITORIES: GEO

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Comparative profiling of chromatin state maps and transcription factor occupancy during human fetal and adult erythropoiesis

Project description:We report the comparative investigation of genome-wide chromatin state maps, transcription factor (TF) occupancy, and gene expression profiles from developing red cell precursors at two developmental stages. Contrasting the similarities and differences between fetal and adult erythropoiesis provides important insights into the erythroid gene expression programs and gene regulatory networks. Specifically, comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that master regulators, such as GATA1 and TAL1, cooperatively act within active enhancers but have little predictive value for stage-specific enhancer activity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of adult-stage expression program. Thus, the combinatorial assembly of master regulators and transcriptional co-regulators at developmental stage-specific enhancers controls gene expression programs and temporal regulation of transcriptional networks in a mammalian genome. Examination of various histone modifications and transcription factor occupancy by ChIP-seq in fetal and adult proerythroblasts.

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Histone H3K27ac separates active from poised enhancers and predicts developmental state (gene expression data)

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2010-10-31 | E-GEOD-23907 | biostudies-arrayexpress

BMP signaling cooperates with GATA factors to govern stage-specific gene expression during erythroid differentiation [ATAC-Seq]

Project description:Hematopoietic progenitors respond to developmental and environmental cues to differentiate. The stage-specific steps of differentiation are stereotypic for each cell lineage, and are controlled by transcription. Here we investigate how differential genomic binding of signal-responsive and lineage-restricted transcription factors can specify subsequent stages of erythropoiesis. Using a human erythroid differentiation system, we extensively characterized the co-operation of the BMP signaling transcription factor SMAD1 with the erythroid transcription factors GATA2 and GATA1 in a detailed time-course. BMP signaling enhances erythroid differentiation. SMAD1 is co-recruited with GATA factors at stage-specific genes that are required to have high expression in each stage. Additionally, we observed SMAD1-GATA co-enriched regions are within super-enhancers and span accessible chromatin. Co-bound regions harbor cell-type specific transcription factor motifs that change during commitment, in contrast to GATA-alone regions. Our studies demonstrate that signal-responsive factors together with lineage regulators mark genomic “hotspots” that function to regulate stage-specific gene expression.

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Transcriptional Signaling Centers Regulate Erythroid Gene Expression and are Disrupted in Common Variations of Human Red Blood Cell Traits

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BMP signaling cooperates with GATA factors to govern stage-specific gene expression during erythroid differentiation [RNA-Seq]

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BMP signaling cooperates with GATA factors to govern stage-specific gene expression during erythroid differentiation [ChIP-Seq]

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Histone H3K27ac separates active from poised enhancers and predicts developmental state (gene expression data)

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Identification of H3 Lysine 4 Monomethylation Associated Proteins at Mammalian Enhancers

Project description:Enhancers act to regulate cell type specific gene expression by facilitating the transcription of target genes. In mammalian cells active or primed enhancers are commonly marked by monomethylation of Histone H3 at lysine 4 (H3K4me1) in a cell-type specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals has been unclear. In the present study, we conducted SILAC Mass-spec experiments with mono-nucleosomes and identified multiple H3K4me1 associated proteins, including proteins involved in chromatin remodeling. We demonstrate that H3K4me1 augments the association of the chromatin remodeling complex BAF to enhancers in vivo. Furthermore we show that in vitro, H3K4me1 nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of a BAF component BAF45c further reveal that monomethylation, but not trimethylation, is accommodated in this protein’s H3K4 binding site. Our results suggest that H3K4me1 plays an active role at enhancers by facilitating the binding of the BAF complex and possibly other chromatin regulators.

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Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes [ChIP-Seq]

Project description:The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs). We report here that the ESC master transcription factors and Mediator form “super-enhancers” at most genes known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4, Sox2, Nanog, Klf4, Esrrb and Mediator. Super-enhancers stimulate considerably higher transcription than typical enhancers in vivo and in reporter vectors. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. These results implicate super-enhancers in the control of mammalian cell identity and differentiation. ChIP-Seq and controls associated with Super-Enhancers in murine cell types

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