Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence.

Autor:	Olan I; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK., Parry AJ; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK.; Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK., Schoenfelder S; Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK., Narita M; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK., Ito Y; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK., Chan ASL; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK., Slater GSC; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK., Bihary D; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK., Bando M; Laboratory of Genome Structure and Function, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan., Shirahige K; Laboratory of Genome Structure and Function, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan., Kimura H; Cell Biology Centre, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan., Samarajiwa SA; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK., Fraser P; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK. pfraser@bio.fsu.edu.; Department of Biological Science, Florida State University, Tallahassee, FL, USA. pfraser@bio.fsu.edu., Narita M; Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK. masashi.narita@cruk.cam.ac.uk.; Tokyo Tech World Research Hub Initiative (WRHI), Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan. masashi.narita@cruk.cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Nov 27; Vol. 11 (1), pp. 6049. Date of Electronic Publication: 2020 Nov 27.
DOI:	10.1038/s41467-020-19878-4
Abstrakt:	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.
Databáze:	MEDLINE
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