Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells.
Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells.
复制标题
DOI：
10.1038/s41467-022-31198-3
复制
发表时间：
2022-06-20
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
异染色质维持基因组的完整性和功能，并被组织成不同的核结构域。其中一些结构域被认为是通过HP1的积累而形成的相分离。小鼠异染色质含有非编码主要卫星重复序列（MSR），在小鼠胚胎干细胞（ESCs）中高度转录。在这里，我们报道了MSR转录本可以在体外驱动HP1液滴的形成，并在ESCs中调节异染色质形成动态凝聚体，从而促进多能细胞特征的大核结构域的形成。消耗MSR转录本导致异染色质转变为更紧密和静态的状态。出乎意料的是，改变异染色质的生物物理特性对胚胎干细胞有严重的影响，包括染色体不稳定和有丝分裂缺陷。这些发现揭示了MSR转录本在调节异染色质的组织和特性以保持基因组稳定性方面的重要作用。他们还提供了可以调节相分离的过程和破坏异染色质凝聚物性质的功能后果的见解。在这里，作者展示了小鼠胚胎干细胞中的卫星转录物在体外驱动HP1α成液滴，并在体内控制HP1α的组织和与染色质的关联。耗尽卫星转录本将异染色质转化为一种较少动态和更多静态的状态，并导致染色体不稳定。
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. Here the authors show satellite transcripts in mouse embryonic stem cells drive HP1α into droplets in vitro and also control HP1α organisation and association with chromatin in vivo. Depleting the satellite transcripts converts heterochromatin into a less dynamic and more static state and leads to chromosome instability.
登录
查看更多内容
影响因子：
16.6
作者：
Ahuja AK;Jodkowska K;Teloni F;Bizard AH;Zellweger R;Herrador R;Ortega S;Hickson ID;Altmeyer M;Mendez J;Lopes M
通讯作者：
Lopes M
影响因子：
14.9
作者：
Cavaluzzi, MJ;Borer, PN
通讯作者：
Borer, PN
影响因子：
2.7
作者：
Aoto, Takahiro;Saitoh, Noriko;Nakao, Mitsuyoshi
通讯作者：
Nakao, Mitsuyoshi
影响因子：
48
作者：
de Chaumont, Fabrice;Dallongeville, Stephane;Olivo-Marin, Jean-Christophe
通讯作者：
Olivo-Marin, Jean-Christophe
影响因子：
56.9
作者：
Festenstein, R;Pagakis, SN;Kioussis, D
通讯作者：
Kioussis, D