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

Tsung-Han S Hsieh; Claudia Cattoglio; Elena Slobodyanyuk; Anders S Hansen; Xavier Darzacq; Robert Tjian

doi:10.1038/s41588-022-01223-8

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

Nat Genet. 2022 Dec;54(12):1919-1932. doi: 10.1038/s41588-022-01223-8. Epub 2022 Dec 5.

Authors

Tsung-Han S Hsieh^{1

2

3

4

5}, Claudia Cattoglio^#^{1

2

3

4}, Elena Slobodyanyuk^#^{1

2}, Anders S Hansen⁶, Xavier Darzacq^{7

8

9

10}, Robert Tjian^{11

12

13

14}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
² Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA, USA.
³ CIRM Center of Excellence, University of California, Berkeley, Berkeley, CA, USA.
⁴ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.
⁵ Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
⁶ Department of Biological Engineering, Massachussets Institute of Technology, Cambridge, MA, USA.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. darzacq@berkeley.edu.
⁸ Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA, USA. darzacq@berkeley.edu.
⁹ CIRM Center of Excellence, University of California, Berkeley, Berkeley, CA, USA. darzacq@berkeley.edu.
¹⁰ Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA. darzacq@berkeley.edu.
¹¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. jmlim@berkeley.edu.
¹² Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA, USA. jmlim@berkeley.edu.
¹³ CIRM Center of Excellence, University of California, Berkeley, Berkeley, CA, USA. jmlim@berkeley.edu.
¹⁴ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA. jmlim@berkeley.edu.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
CCCTC-Binding Factor / genetics
Cohesins
Mice
Proteins*

Substances

CCCTC-Binding Factor
Proteins
WAPL protein, mouse
Ctcf protein, mouse
Yy1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding