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

First Author  Ren G Year  2017
Journal  Mol Cell Volume  67
Issue  6 Pages  1049-1058.e6
PubMed ID  28938092 Mgi Jnum  J:251945
Mgi Id  MGI:6106788 Doi  10.1016/j.molcel.2017.08.026
Citation  Ren G, et al. (2017) CTCF-Mediated Enhancer-Promoter Interaction Is a Critical Regulator of Cell-to-Cell Variation of Gene Expression. Mol Cell 67(6):1049-1058.e6
abstractText  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.
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