Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Mol Cell. 2022 Jan 6;82(1):106-122.e9. doi: 10.1016/j.molcel.2021.11.011. Epub 2021 Dec 6.
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.
染色质的紧密调控突出了早期胚胎程序的保真度。然而，染色质是如何组织起来防止发育程序的逆转尚不清楚。具体来说，全能性到多能性的转变标志着染色质的最显著事件之一，但这一过程中组蛋白改变的性质尚未完全描述。在这里，我们表明连接组蛋白 H1 被 SUMO2/3 进行翻译后修饰，这有利于其在胚胎干细胞（ESCs）中超浓缩异染色质上的固定。在 SUMOylation 耗尽后，染色质变得疏松，H1 被逐出，导致全能性重新激活。此外，我们表明 H1 和 SUMO2/3 共同介导对全能性元件的抑制。最后，我们证明阻止 H1 上的 SUMOylation 会削弱其在 ESCs 中抑制全能性程序的能力。总的来说，我们的研究结果揭示了 H1 的 SUMOylation 在促进染色质抑制和消除全能性身份方面的关键作用。
