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Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells.
Novo, Clara Lopes; Wong, Emily V; Hockings, Colin; Poudel, Chetan; Sheekey, Eleanor; Wiese, Meike; Okkenhaug, Hanneke; Boulton, Simon J; Basu, Srinjan; Walker, Simon; Kaminski Schierle, Gabriele S; Narlikar, Geeta J; Rugg-Gunn, Peter J.
Afiliação
  • Novo CL; Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK. clara.novo@gmail.com.
  • Wong EV; Tommy's National Miscarriage Research Centre at Imperial College London, London, W12 0NN, UK. clara.novo@gmail.com.
  • Hockings C; The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK. clara.novo@gmail.com.
  • Poudel C; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
  • Sheekey E; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK.
  • Wiese M; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB3 0AS, UK.
  • Okkenhaug H; Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
  • Boulton SJ; Wellcome - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, UK.
  • Basu S; Imaging Facility, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
  • Walker S; The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
  • Kaminski Schierle GS; Artios Pharma Ltd., B940, Babraham Research Campus, Cambridge, CB22 3FH, UK.
  • Narlikar GJ; Wellcome - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, UK.
  • Rugg-Gunn PJ; Imaging Facility, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Nat Commun ; 13(1): 3525, 2022 06 20.
Article em En | MEDLINE | ID: mdl-35725842
Heterochromatin maintains genome integrity and function, and is organised into distinct nuclear domains. Some of these domains are proposed to form by phase separation through the accumulation of HP1ɑ. Mouse heterochromatin contains noncoding major satellite repeats (MSR), which are highly transcribed in mouse embryonic stem cells (ESCs). Here, we report that MSR transcripts can drive the formation of HP1ɑ droplets in vitro, and modulate heterochromatin into dynamic condensates in ESCs, contributing to the formation of large nuclear domains that are characteristic of pluripotent cells. Depleting MSR transcripts causes heterochromatin to transition into a more compact and static state. Unexpectedly, changing heterochromatin's biophysical properties has severe consequences for ESCs, including chromosome instability and mitotic defects. These findings uncover an essential role for MSR transcripts in modulating the organisation and properties of heterochromatin to preserve genome stability. They also provide insights into the processes that could regulate phase separation and the functional consequences of disrupting the properties of heterochromatin condensates.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Heterocromatina / Células-Tronco Embrionárias Murinas Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Heterocromatina / Células-Tronco Embrionárias Murinas Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article