Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1

<jats:title>Abstract</jats:title><jats:p>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...

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Main Authors: Hsieh, Tsung-Han S, Cattoglio, Claudia, Slobodyanyuk, Elena, Hansen, Anders S, Darzacq, Xavier, Tjian, Robert
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2023
Online Access:https://hdl.handle.net/1721.1/147833
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author Hsieh, Tsung-Han S
Cattoglio, Claudia
Slobodyanyuk, Elena
Hansen, Anders S
Darzacq, Xavier
Tjian, Robert
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Hsieh, Tsung-Han S
Cattoglio, Claudia
Slobodyanyuk, Elena
Hansen, Anders S
Darzacq, Xavier
Tjian, Robert
author_sort Hsieh, Tsung-Han S
collection MIT
description <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
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spelling mit-1721.1/1478332023-02-02T03:25:43Z Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1 Hsieh, Tsung-Han S Cattoglio, Claudia Slobodyanyuk, Elena Hansen, Anders S Darzacq, Xavier Tjian, Robert Massachusetts Institute of Technology. Department of Biological Engineering <jats:title>Abstract</jats:title><jats:p>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.</jats:p> 2023-02-01T17:31:30Z 2023-02-01T17:31:30Z 2022-12 2023-02-01T17:12:05Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147833 Hsieh, Tsung-Han S, Cattoglio, Claudia, Slobodyanyuk, Elena, Hansen, Anders S, Darzacq, Xavier et al. 2022. "Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1." Nature Genetics, 54 (12). en 10.1038/s41588-022-01223-8 Nature Genetics Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle Hsieh, Tsung-Han S
Cattoglio, Claudia
Slobodyanyuk, Elena
Hansen, Anders S
Darzacq, Xavier
Tjian, Robert
Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title_full Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title_fullStr Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title_full_unstemmed Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title_short Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
title_sort enhancer promoter interactions and transcription are largely maintained upon acute loss of ctcf cohesin wapl or yy1
url https://hdl.handle.net/1721.1/147833
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