Enhancer-promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1.
Tsung-Han S HsiehClaudia CattoglioElena SlobodyanyukAnders S HansenXavier DarzacqRobert Tse Nan TjianPublished in: Nature genetics (2022)
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.
Keyphrases
- transcription factor
- single molecule
- liver failure
- gene expression
- high resolution
- respiratory failure
- dna methylation
- dna binding
- genome wide
- drug induced
- aortic dissection
- binding protein
- embryonic stem cells
- single cell
- dna damage
- genome wide identification
- hepatitis b virus
- intensive care unit
- atomic force microscopy
- living cells