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

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

PROVIDER: PRJNA966131 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24401756_1.fastq.gz	Fastqsanger.gz
	SRR24401756_2.fastq.gz	Fastqsanger.gz
	SRR24401757_1.fastq.gz	Fastqsanger.gz
	SRR24401757_2.fastq.gz	Fastqsanger.gz
	SRR24401758_1.fastq.gz	Fastqsanger.gz

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

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

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

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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.

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Reprogramming of 3D genome structure underlying HSPC development in zebrafish [HiC]

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

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Reprogramming of 3D genome structure underlying HSPC development in zebrafish [HiC]

Project description:Development of hematopoietic stem and progenitor cells (HSPC) is a multi-staged complex process that conserved between zebrafish and mammals; however, the mechanism underlying HSPC development is not fully understood. Chromatin conformation plays important roles in transcriptional regulation and cell fate decision, its dynamic and role in HSPC development is poorly investigated.Here, we performed chromatin structure and multi-omics dissection across different stages of HSPC developmental trajectory in zebrafish. Chromatin organization of zebrafish resemble mammalian cells with similar hierarchical structure and characteristics. We revealed the multi-scale reorganization of 3D genome and its influence on transcriptional regulation and transition of cell function during HSPC development. Nascent HSPC is featured by loose conformation with obscure structure at all layers. Notably, PU.1 was identified as a potential factor mediating formation of promoter-involved loops and regulating gene expression as well as HSPC function. Our results provided a global view of chromatin structure dynamics associated with development of zebrafish HSPC and discovered key transcription factor involved in HSPC chromatin interactions, which will provide new insights into the epigenetic regulatory mechanisms underlying vertebrate HSPC fate decision.

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

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