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Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231486 | GEO | 2023/08/21

REPOSITORIES: GEO

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Genome-wide transcription factor-binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs.

Project description:Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac, HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (heptad, PU.1, CTCF, STAG2) in HSPC subsets (stem/multipotent progenitors plus common myeloid, granulocyte macrophage, and megakaryocyte erythrocyte progenitors) and found TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs, including PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type-specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of TF complexes was at least partially regulated by features encoded in DNA sequence motifs. Taken together, this study comprehensively characterizes the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying data sets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analyzing aberrant regulatory networks in leukemic cells.

| S-EPMC10651876 | biostudies-literature

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiC]

Project description:Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay of transcription factors (TFs) to regulate their differentiation into mature blood cells. A heptad of TFs - FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2 - has been shown to bind to regulatory elements in bulk CD34+ HSPCs. However, whether specific combinations of these TFs have distinct roles in regulating hematopoietic differentiation remained unknown. In this study, we mapped the genome-wide binding profiles of these TFs and other chromatin-associated markers in distinct HSPC subsets (HSC, CMP, GMP, MEP). We found that the heptad occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type specific gene expression. Moreover, we observed distinct regulatory elements that were enriched with specific combinations of TFs, such as stem-cell specific elements with ERG, and myeloid and megakaryocyte-erythroid specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. These findings suggest that specific combinations of TFs play critical roles in the regulation of hematopoietic differentiation, and provide a valuable resource for the development of targeted therapies to manipulate specific HSPC subsets.

2023-08-21 | GSE231485 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiChIP]

2023-08-21 | GSE231426 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIPmentation]

2023-08-21 | GSE231422 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIP-seq]

2023-08-21 | GSE231425 | GEO

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC

Project description:Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC

| PRJNA966119 | ENA

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiC]

Project description:Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiC]

| PRJNA966131 | ENA

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiChIP]

Project description:Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [HiChIP]

| PRJNA965792 | ENA

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIPmentation]

Project description:Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIPmentation]

| PRJNA965795 | ENA

Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIP-seq]

Project description:Genome-wide Transcription Factor binding maps reveal cell-specific changes in the regulatory architecture of human HSPC [ChIP-seq]

| PRJNA965793 | ENA

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