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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE131055 | GEO | 2021/01/18

REPOSITORIES: GEO

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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

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

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

| PRJNA542478 | ENA

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]

| PRJNA542482 | ENA

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]

| PRJNA542480 | ENA

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]

| PRJNA542481 | ENA

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 binding directly mediates interactions among cis-regulatory elements essential for hematopoiesis.

Project description:While constitutive CCCTC-binding factor (CTCF)-binding sites are needed to maintain relatively invariant chromatin structures, such as topologically associating domains, the precise roles of CTCF to control cell-type-specific transcriptional regulation remain poorly explored. We examined CTCF occupancy in different types of primary blood cells derived from the same donor to elucidate a new role for CTCF in gene regulation during blood cell development. We identified dynamic, cell-type-specific binding sites for CTCF that colocalize with lineage-specific transcription factors. These dynamic sites are enriched for single-nucleotide polymorphisms that are associated with blood cell traits in different linages, and they coincide with the key regulatory elements governing hematopoiesis. CRISPR-Cas9-based perturbation experiments demonstrated that these dynamic CTCF-binding sites play a critical role in red blood cell development. Furthermore, precise deletion of CTCF-binding motifs in dynamic sites abolished interactions of erythroid genes, such as RBM38, with their associated enhancers and led to abnormal erythropoiesis. These results suggest a novel, cell-type-specific function for CTCF in which it may serve to facilitate interaction of distal regulatory emblements with target promoters. Our study of the dynamic, cell-type-specific binding and function of CTCF provides new insights into transcriptional regulation during hematopoiesis.

| S-EPMC7955410 | biostudies-literature

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