RT Journal Article SR Electronic T1 Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.14.452365 DO 10.1101/2021.07.14.452365 A1 Tsung-Han S. Hsieh A1 Claudia Cattoglio A1 Elena Slobodyanyuk A1 Anders S. Hansen A1 Xavier Darzacq A1 Robert Tjian YR 2021 UL http://biorxiv.org/content/early/2021/07/14/2021.07.14.452365.abstract AB It remains unclear why acute depletion of CTCF and cohesin only marginally affects expression of most genes despite substantially perturbing 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 to find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-hour) depletion of CTCF, cohesin, and WAPL. YY1 has been proposed to be 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 binding to chromatin. Thus, although neither CTCF, cohesin, WAPL, nor YY1 are required for the short-term maintenance of most E-P interactions and gene expression, we propose that cohesin may serve as a “transcription factor binding platform” that facilitates transcription factor binding to chromatin.Competing Interest StatementThe authors have declared no competing interest.