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CTCF-mediated enhancer-promoter interaction is a critical regulator of cell-to-cell variation of gene expression

ABSTRACT: Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically-associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers. Deletion of CTCF sites using CRISPR/Cas9 compromises enhancer-promoter interactions. Using single-cell flow cytometry and single-molecule RNA-FISH assays, we demonstrate that knocking down of CTCF or deletion of a CTCF binding site results in increased cell-to-cell variation of gene expression, indicating that long-range promoter-enhancer interaction mediated by CTCF plays an important role in controlling the cell-to-cell variation of gene expression in mammalian cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE66343 | GEO | 2017/10/01

SECONDARY ACCESSION(S): PRJNA276568

REPOSITORIES: GEO

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