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Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells

By Clara Lopes Novo, Emily Wong, Colin Hockings, Chetan Poudel, Eleanor Sheekey, Simon Walker, Gabriele S. Kaminski Schierle, Geeta J. Narlikar, Peter J. Rugg-Gunn

Posted 08 Jun 2020
bioRxiv DOI: 10.1101/2020.06.08.139642

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 HP1a. Mammalian 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 HP1a droplets in vitro, and scaffold heterochromatin into dynamic condensates in ESCs, leading 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 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 new insights into the processes that could regulate phase separation and the functional consequences of disrupting the properties of heterochromatin condensates. ### Competing Interest Statement The authors have declared no competing interest.

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