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Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development

ABSTRACT: Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development

PROVIDER: PRJNA542478 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13454132.fastq.gz	Fastqsanger.gz
	SRR13454133.fastq.gz	Fastqsanger.gz
	SRR13454134.fastq.gz	Fastqsanger.gz
	SRR13454135.fastq.gz	Fastqsanger.gz
	SRR13454136.fastq.gz	Fastqsanger.gz

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Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [HiChIP]

Project description:Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [HiChIP]

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Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ATAC-seq]

Project description:Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ATAC-seq]

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Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ChIP-seq]

Project description:Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ChIP-seq]

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Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [Capture Hi-C]

Project description:Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [Capture Hi-C]

| PRJNA543246 | ENA

Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [HiChIP]

Project description:The ubiquitously expressed transcription factor CTCF maintains higher-order chromatin structure in multiple cell types and species through well-established common mechanisms. Here we define a new role for CTCF in tissue-specific gene regulation revealed by serial examinations of genome-wide CTCF occupancy during red blood cell (RBC) differentiation of human CD34+ hematopoietic stem/progenitor cells (HSPCs). We identified 1753 dynamic, erythroid developmental stage-specific CTCF chromatin occupancy sites that occur through both direct DNA binding and indirectly via interactions with lineage-specific transcription factors. These dynamic sites display features of transcriptional enhancers, function as hubs of cis-regulatory elements (CREs) interactome, and are enriched for single nucleotide polymorphisms (SNPs) associated with RBC traits. Precise deletion of CTCF binding motifs from those dynamically bound sites alternated local CRE-interactions and disrupted erythropoiesis. Our study highlights novel, lineage-specific functions for CTCF and provides new insights into how genetic variation regulates erythropoiesis

2021-01-18 | GSE131054 | GEO

Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ATAC-seq]

2021-01-18 | GSE131053 | GEO

Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [ChIP-seq]

2021-01-18 | GSE131052 | GEO

Dynamic CTCF occupancy during differentiation rewires cis-regulatory module interactions essential for development [Capture Hi-C]

2021-01-18 | GSE131324 | GEO

Acute depletion of CTCF rewires genome-wide chromatin accessibility

Project description:The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription. Here we systematically integrated multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, CRISPR-Cas9 survival dropout screening, time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewired genome-wide chromatin accessibility. Increased accessible chromatin regions were largely located adjacent to CTCF-binding sites at promoter regions and insulator sites and were associated with enhanced transcription of nearby genes. In addition, we used CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners in regulating downstream gene expression. We successfully identified 40 candidates, including multiple established partners (i.e., MYC) supported by all layers of evidence. Interestingly, many CTCF co-regulators (e.g., YY1, ZBTB7A) that have evident alterations of respective downstream gene expression do not show changes at their expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription. This study highlights CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation

2021-07-04 | PXD026484 | Pride

Acute depletion of CTCF rewires genome-wide chromatin accessibility

Project description:Accumulated data suggest that transcription factor CTCF is indispensable to define topologically associated domain (TAD) boundaries and to maintain intra-TAD chromatin loop structures. However, upon genome-wide acute depletion of CTCF, the discrepancy between global reduction of chromatin interactions and minimal alteration of transcription has been evidently observed. To understand CTCF’s direct role in chromatin accessibility and global transcriptional regulation, we have systematically integrated data collected from ATAC-seq, RNA-seq, whole genome bisulfite-seq, Cut&Run and HiC in a previously established CTCF-miniAID knock-in cell lines. Acute degradation of CTCF markedly rewires genome-wide chromatin accessibility but not DNA methylation. Differentially altered ATAC-seq peaks are highly associated with adjacent CTCF binding sites, supporting the direct link between CTCF occupancy and its surrounding chromatin accessibility. Increased ATAC-seq peaks upon CTCF loss are notably associated with enhanced transcription at promoter regions and insulator sites, while decreased ATAC-seq peaks are significantly enriched at DNA loops. Furthermore, using CTCF associated multi-Omics data we have established a combinatorial data analysis pipeline to discover novel CTCF mediated insulators in the genome, by which we have successfully identified 67 novel insulators at non-coding regions distal to promoters. Functional CRISPR interference (CRISPRi) unconstrained the repressive transcriptional regulation of target genes. In sum, using CTCF acute depletion cell model and multi-Omics analysis, we concluded that CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role for transcriptional regulation.

2021-08-26 | GSE153237 | GEO

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