期刊
NATURE GENETICS
卷 54, 期 12, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-022-01223-8
关键词
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资金
- California Institute of Regenerative Medicine [LA1-08013]
- Koret UC Berkeley-Tel Aviv University Initiative grant
- Howard Hughes Medical Institute [003061]
- NIH [R00GM130896, DP2GM140938, R33CA257878]
- NSF [2036037]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [2036037] Funding Source: National Science Foundation
Short-term maintenance of most gene expression and enhancer-promoter interactions does not require CTCF, Cohesin, WAPL, or YY1, but Cohesin may facilitate transcription factor binding to targets more efficiently.
It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-h) depletion of CTCF, cohesin or WAPL. YY1 has been proposed as a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription and 3D genome folding. Strikingly, live-cell, single-molecule imaging revealed that cohesin depletion reduced transcription factor (TF) binding to chromatin. Thus, although CTCF, cohesin, WAPL or YY1 is not required for the short-term maintenance of most E-P interactions and gene expression, our results suggest that cohesin may facilitate TFs to search for and bind their targets more efficiently.
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