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CTCF-Mediated Enhancer-Promoter Interaction Is a Critical Regulator of Cell-to-Cell Variation of Gene Expression.

Molecular cell | Sep 21, 2017

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 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 important roles in controlling the cell-to-cell variation of gene expression in mammalian cells.

Pubmed ID: 28938092 RIS Download

Mesh terms: Animals | Binding Sites | CCCTC-Binding Factor | CD4-Positive T-Lymphocytes | CRISPR-Cas Systems | Cell Line, Tumor | Enhancer Elements, Genetic | Female | Flow Cytometry | Gene Expression Regulation | High-Throughput Nucleotide Sequencing | In Situ Hybridization, Fluorescence | Mice, Inbred C57BL | Promoter Regions, Genetic | Protein Binding | RNA Interference | Repressor Proteins | Single-Cell Analysis | Transcription, Genetic | Transcriptional Activation | Transfection

Data used in this publication

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Associated grants

  • Agency: Intramural NIH HHS, Id: ZIA HL006030-07

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