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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Language: | English |
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Springer Science and Business Media LLC
2023
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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> |
first_indexed | 2024-09-23T12:42:00Z |
format | Article |
id | mit-1721.1/147833 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T12:42:00Z |
publishDate | 2023 |
publisher | Springer Science and Business Media LLC |
record_format | dspace |
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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