Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence

Ioana Olan, Aled J. Parry, Stefan Schoenfelder, Masako Narita, Yoko Ito, Adelyne S. L. Chan, Guy St.C. Slater, Dóra Bihary, Masashige Bando, Katsuhiko Shirahige, Hiroshi Kimura, Shamith A. Samarajiwa, Peter Fraser () and Masashi Narita ()
Additional contact information
Ioana Olan: Cancer Research UK Cambridge Institute, University of Cambridge
Aled J. Parry: Cancer Research UK Cambridge Institute, University of Cambridge
Stefan Schoenfelder: Epigenetics Programme, The Babraham Institute, Babraham Research Campus
Masako Narita: Cancer Research UK Cambridge Institute, University of Cambridge
Yoko Ito: Cancer Research UK Cambridge Institute, University of Cambridge
Adelyne S. L. Chan: Cancer Research UK Cambridge Institute, University of Cambridge
Guy St.C. Slater: Cancer Research UK Cambridge Institute, University of Cambridge
Dóra Bihary: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus
Masashige Bando: Laboratory of Genome Structure and Function, Institute of Molecular and Cellular Biosciences, The University of Tokyo
Katsuhiko Shirahige: Laboratory of Genome Structure and Function, Institute of Molecular and Cellular Biosciences, The University of Tokyo
Hiroshi Kimura: Cell Biology Centre, Institute of Innovative Research, Tokyo Institute of Technology
Shamith A. Samarajiwa: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus
Peter Fraser: Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus
Masashi Narita: Cancer Research UK Cambridge Institute, University of Cambridge

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Senescence is a state of stable proliferative arrest, generally accompanied by the senescence-associated secretory phenotype, which modulates tissue homeostasis. Enhancer-promoter interactions, facilitated by chromatin loops, play a key role in gene regulation but their relevance in senescence remains elusive. Here, we use Hi-C to show that oncogenic RAS-induced senescence in human diploid fibroblasts is accompanied by extensive enhancer-promoter rewiring, which is closely connected with dynamic cohesin binding to the genome. We find de novo cohesin peaks often at the 3′ end of a subset of active genes. RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. Similar IL1B induction with de novo cohesin appearance and new loop formation are observed in terminally differentiated macrophages, but not TNFα-treated cells. These results suggest that RAS-induced senescence represents a cell fate determination-like process characterised by a unique gene expression profile and 3D genome folding signature, mediated in part through cohesin redistribution on chromatin.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19878-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19878-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19878-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().