SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity

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Molecular Cell. 2022 Jul;82:106-122.e9. doi: https://doi.org/10.1016/j.molcel.2021.11.011

SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity Aguilera Castrejon Lab

Sheban Daoud, Shani Tom, Maor Roey, Aguilera-Castrejon Alejandro, Mor Nofar, Oldak Bernardo, Shmueli Merav, Eisenberg-Lerner Avital, Bayerl Jonathan, Hebert Jakob, Viukov Sergey, Chen Guoyun, Kacen Assaf, Krupalnik Vladislav, Chugaeva Valeriya, Tarazi Shadi, Rodríguez-delaRosa Alejandra, Zerbib Mirie, Ulman Adi, Masarwi Solaiman, Kupervaser Meital, Levin Yishai, Shema Efrat, David Yael, Novershtern Noa, Hanna Jacob, Merbl Yifat

Note: Research in this publication was not performed at Janelia.

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Abstract

Summary 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.

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SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity

Note: Research in this publication was not performed at Janelia.

Abstract

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