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Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE94452 | GEO | 2018/05/01

REPOSITORIES: GEO

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Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation.

Project description:The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.

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Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation IV

Project description:The CCCTC-binding factor (CTCF) is widely regarded as a key player in chromosome organization in mammalian cells, yet direct assessment of its role in genome architecture and gene regulation has been difficult. Here, we use auxin-inducible degron techniques to acutely deplete CTCF to determine how loss of CTCF affect chromatin organization and gene expression. In mouse embryonic stem cells, depletion of CTCF results in rapid loss of chromatin loops anchored at CTCF-binding sites without major disruption to chromatin compartments and topological domains. In the absence of CTCF, many lineage-specific genes fail to express properly during differentiation to neural precursor cells, but transcriptional regulation of most genes is unaffected. Genes dependent on CTCF for induction are generally bound by the factor at promoters, which are connected to distal enhancers via CTCF-dependent chromatin loops. By contrast, CTCF-independent genes generally lack CTCF binding at the promoter and are generally closer to enhancers. These results refine our understanding of CTCF function in chromatin organization and gene regulation.

2020-03-06 | GSE146454 | GEO