RNA interactions are essential for proper CTCF function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA517076 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8487480.fastq.gz | Fastqsanger.gz | |||
| SRR8487490.fastq.gz | Fastqsanger.gz | |||
| SRR8487500_1.fastq.gz | Fastqsanger.gz | |||
| SRR8487500_2.fastq.gz | Fastqsanger.gz | |||
| SRR8487481.fastq.gz | Fastqsanger.gz |
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Project description:The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms by which CTCF dynamically contributes to genome organization are not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs, promoting its self-association. In this regard, we now report two independent features that disrupt CTCF association with chromatin: inhibition of transcription and disruption of CTCF-RNA interactions through mutations of two of its 11 zinc fingers which are not required for CTCF binding to its cognate DNA site: zinc finger-1 (ZF1) or -10 (ZF10). These mutations alter gene expression profiles as CTCF mutants lose their ability to form chromatin loops and thus, the ability to insulate chromatin domains as well as mediate CTCF long-range genomic interactions. Our results point to the importance of CTCF-mediated RNA interactions as a structural component of genome organization.
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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
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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
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