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Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis [Cap-C]

ABSTRACT: Mammalian erythroid cells development can be divided into three period: hematopoietic stem and progenitor cells (HSPC), erythroid progenitor (Ery-Pro) and erythroid precursor (Ery-Pre). To better understand human erythropoiesis and its regulation, we performed genome-wide studies of chromatin architecture, enhancer and select transcription factors binding, and transcriptomics profiling utilizing modified strategy to obtain defined progenitor and precursor populations from primary human erythroid cells. Integration and analysis of these data reveals that the TAD structure is stable but promoter - enhancer interactions are highly dynamic in a stage specific manner. Erythroid master regulator - GATA1 involves in the P-E interactions stepwisely. GATA1 binding is largely stable in erythroid progenitor and precursor, but dynamic GATA1 binding during this process regulate a productive erythroid gene expression and local chromatin rewiring. Additionally, we also have showed that dosage of GATA1 control the erythroid progenitor behavior and the erythroid progression. The valuable chromatin architecture and epigenome data will provide more comprehensive insight of human erythropoiesis and dynamic gene regulation of cellular differentiation even more broadly.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214806 | GEO | 2023/05/07

REPOSITORIES: GEO

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Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis [scRNA-seq]

Project description:Mammalian erythroid cells development can be divided into three period: hematopoietic stem and progenitor cells (HSPC), erythroid progenitor (Ery-Pro) and erythroid precursor (Ery-Pre). To better understand human erythropoiesis and its regulation, we performed genome-wide studies of chromatin architecture, enhancer and select transcription factors binding, and transcriptomics profiling utilizing modified strategy to obtain defined progenitor and precursor populations from primary human erythroid cells. Integration and analysis of these data reveals that the TAD structure is stable but promoter - enhancer interactions are highly dynamic in a stage specific manner. Erythroid master regulator - GATA1 involves in the P-E interactions stepwisely. GATA1 binding is largely stable in erythroid progenitor and precursor, but dynamic GATA1 binding during this process regulate a productive erythroid gene expression and local chromatin rewiring. Additionally, we also have showed that dosage of GATA1 control the erythroid progenitor behavior and the erythroid progression. The valuable chromatin architecture and epigenome data will provide more comprehensive insight of human erythropoiesis and dynamic gene regulation of cellular differentiation even more broadly.

2023-05-07 | GSE214810 | GEO

Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis [RNA-seq]

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Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis [MicroC]

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Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis [HiChIP]

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GATA factor-mediated gene regulation in human erythropoiesis (RNA-Seq)

Project description:Human erythropoiesis is a stepwise process in which multipotent hematopoietic stem/progenitor cells (HSPC) are initially committed towards the erythroid lineage and then differentiated into mature erythroid precursors. Commitment and differentiation are tightly regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Although the role of GATA factors in erythropoiesis has been extensively studied, how they regulate transcription from early to late stages of human erythropoiesis still remains underinvestigated. Here, we investigated GATA-mediated transcriptional regulation along erythroid development through the integrative analysis of gene expression, chromatin modifications, and GATA factors’ binding in human HSPC, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation, a mark of active regulatory elements, and diminished usage of active enhancers and super-enhancers was observed during erythroid lineage commitment and differentiation. We found that GATA factors mediate the transcriptional changes occurring during erythropoiesis through a stage-specific interplay with regulatory elements. In particular, GATA1 binds different sets of regulatory elements in early progenitors and late precursors, and controls the transcription of distinct genes in commitment and differentiation. By Chromosome Conformation Capture and CRISPR/Cas9-mediated genome editing, we demonstrated that the binding of GATA1 to a stage-specific super-enhancer sustains the expression of the stem cell factor receptor KIT in human erythroid progenitors. This study provides insights into the dynamics of epigenetic and transcriptional interactions during erythroid development and highlights a new layer of GATA1-mediated regulation in erythropoiesis.

2020-04-10 | GSE124164 | GEO

GATA factor-mediated gene regulation in human erythropoiesis (ChIP-Seq)

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In vitro erythropoiesis at different pO2 induces adaptations that are independent of prior systemic exposure to hypoxia

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2022-04-06 | PXD031776 | Pride

Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis

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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis [RNA-seq]

2023-07-31 | GSE183992 | GEO

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