Histone modifications regulate pioneer transcription factor cooperativity.
Histone modifications regulate pioneer transcription factor cooperativity.
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组蛋白修饰调节先锋转录因子的合作。
DOI：
10.1038/s41586-023-06112-6
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发表时间：
2023-07
期刊：
影响因子：
64.8
通讯作者：
Halic, Mario
中科院分区：
文献类型：
--
作者：
Sinha, Kalyan K. K.;Bilokapic, Silvija;Du, Yongming;Malik, Deepshikha;Halic, Mario
先锋转录因子具有接近紧密染色质中的DNA的能力。多个转录因子可以以合作的方式结合在一起到调节元件，并且先锋转录因子OCT 4（也称为POU 5 F1）和SOX 2之间的合作对于多能性和重编程是重要的。然而，先驱转录因子在染色质上发挥作用和合作的分子机制仍不清楚。在这里，我们提出了冷冻电子显微镜结构的人OCT 4绑定到一个核小体含有人类LIN 28 B或nMATN 1 DNA序列，这两个轴承多个结合位点的OCT 4。我们的结构和生物化学数据表明，OCT 4的结合诱导核小体结构的变化，重新定位核小体DNA，并促进额外的OCT 4和SOX 2的内部结合位点的合作结合。OCT 4的柔性激活结构域接触组蛋白H4的N-末端尾部，改变其构象，从而促进染色质解压缩。此外，OCT 4的DNA结合结构域与组蛋白H3的N-末端尾部接合，并且H3 K27处的翻译后修饰调节DNA定位并影响转录因子协同性。因此，我们的研究结果表明，表观遗传景观可以调节OCT 4活性，以确保适当的细胞编程。人先锋转录因子OCT 4与含有内源性DNA序列的核小体的结合引起核小体结构的变化，并促进多个先锋转录因子的协同组装，这是一种可受组蛋白修饰影响的性质。
Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation between the pioneer transcription factors OCT4 (also known as POU5F1) and SOX2 is important for pluripotency and reprogramming. However, the molecular mechanisms by which pioneer transcription factors function and cooperate on chromatin remain unclear. Here we present cryo-electron microscopy structures of human OCT4 bound to a nucleosome containing human LIN28B or nMATN1 DNA sequences, both of which bear multiple binding sites for OCT4. Our structural and biochemistry data reveal that binding of OCT4 induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional OCT4 and of SOX2 to their internal binding sites. The flexible activation domain of OCT4 contacts the N-terminal tail of histone H4, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA-binding domain of OCT4 engages with the N-terminal tail of histone H3, and post-translational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our findings suggest that the epigenetic landscape could regulate OCT4 activity to ensure proper cell programming. Binding of the human pioneer transcription factor OCT4 to nucleosomes containing endogenous DNA sequences causes changes to the nucleosome structure and facilitates the cooperative assembly of multiple pioneer transcription factors, a property that can be affected by histone modifications.
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影响因子：
16.8
作者：
Bilokapic S;Strauss M;Halic M
通讯作者：
Halic M
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
7.7
作者：
King HW;Klose RJ
通讯作者：
Klose RJ
影响因子：
30.8
作者：
Donaghey J;Thakurela S;Charlton J;Chen JS;Smith ZD;Gu H;Pop R;Clement K;Stamenova EK;Karnik R;Kelley DR;Gifford CA;Cacchiarelli D;Rinn JL;Gnirke A;Ziller MJ;Meissner A
通讯作者：
Meissner A
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH