SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity.
SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity.
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DOI：
10.1016/j.molcel.2021.11.011
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发表时间：
2021-12
期刊：
影响因子：
16
通讯作者：
D. Sheban;Tom Shani;Roey Maor;Alejandro Aguilera-Castrejon;Nofar Mor;Bernardo Oldak;Merav D. Shmueli;Avital Eisenberg-Lerner;Jonathan Bayerl;J. Hebert;Sergey V. Viukov;Guoyun Chen;Assaf Kacen;V. Krupalnik;V. Chugaeva;Shadi Tarazi;Alejandra Rodríguez-delaRosa;Mirie Zerbib;Adi Ulman;Solaiman Masarwi;Meital Kupervaser;Y. Levin;E. Shema;Yael David;Noa Novershtern;J. Hanna;Y. Merbl
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文献类型：
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作者：
D. Sheban;Tom Shani;Roey Maor;Alejandro Aguilera-Castrejon;Nofar Mor;Bernardo Oldak;Merav D. Shmueli;Avital Eisenberg-Lerner;Jonathan Bayerl;J. Hebert;Sergey V. Viukov;Guoyun Chen;Assaf Kacen;V. Krupalnik;V. Chugaeva;Shadi Tarazi;Alejandra Rodríguez-delaRosa;Mirie Zerbib;Adi Ulman;Solaiman Masarwi;Meital Kupervaser;Y. Levin;E. Shema;Yael David;Noa Novershtern;J. Hanna;Y. Merbl
早期胚胎程序的精确性是由染色质的严格调节所强调的。然而，染色质是如何组织起来阻止发育程序逆转的仍然不清楚。具体来说，全能性到多能性的转变标志着染色质最引人注目的事件之一，然而，这一过程背后的组蛋白改变的性质是不完全的特征。在这里，我们表明，连接器组蛋白H1是post-acetonically调制的SUMO 2/3，这有利于其固定到超浓缩的异染色质在胚胎干细胞（ESC）。在SUMO化耗尽时，染色质变得去压缩并且H1被驱逐，导致全能性再激活。此外，我们表明，H1和SUMO 2/3共同介导的全能元素的镇压。最后，我们证明，阻止SUMO化H1废除其抑制全能性计划在胚胎干细胞的能力。总的来说，我们的研究结果揭示了H1 SUMO化在促进染色质抑制和全能性特征破坏方面的关键作用。
The fidelity of the early embryonic program is underlined by tight regulation of the chromatin. Yet, how the chromatin is organized to prohibit the reversal of the developmental program remains unclear. Specifically, the totipotency-to-pluripotency transition marks one of the most dramatic events to the chromatin, and yet, the nature of histone alterations underlying this process is incompletely characterized. Here, we show that linker histone H1 is post-translationally modulated by SUMO2/3, which facilitates its fixation onto ultra-condensed heterochromatin in embryonic stem cells (ESCs). Upon SUMOylation depletion, the chromatin becomes de-compacted and H1 is evicted, leading to totipotency reactivation. Furthermore, we show that H1 and SUMO2/3 jointly mediate the repression of totipotent elements. Lastly, we demonstrate that preventing SUMOylation on H1 abrogates its ability to repress the totipotency program in ESCs. Collectively, our findings unravel a critical role for SUMOylation of H1 in facilitating chromatin repression and desolation of the totipotent identity.