Histone H3.3 phosphorylation amplifies stimulation-induced transcription.
Histone H3.3 phosphorylation amplifies stimulation-induced transcription.
复制标题
组蛋白 H3.3 磷酸化会放大刺激诱导的转录。
DOI：
10.1038/s41586-020-2533-0
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发表时间：
2020-07
期刊：
影响因子：
64.8
通讯作者：
Josefowicz SZ
中科院分区：
文献类型：
--
作者：
Armache A;Yang S;Martínez de Paz A;Robbins LE;Durmaz C;Cheong JQ;Ravishankar A;Daman AW;Ahimovic DJ;Klevorn T;Yue Y;Arslan T;Lin S;Panchenko T;Hrit J;Wang M;Thudium S;Garcia BA;Korb E;Armache KJ;Rothbart SB;Hake SB;Allis CD;Li H;Josefowicz SZ
复杂的生物体能够快速诱导选择基因以响应不同的环境线索。这种调节发生在组蛋白浓缩成染色质的大基因组的背景下。巨噬细胞对病原体感测的反应迅速地参与保守的信号传导途径和转录因子，以协调炎症基因诱导。组蛋白H3.3（祖先组蛋白H3变体）的富集整合是动态调节的染色质和转录的一般特征。然而，很少有人知道染色质是如何在快速诱导基因的调控，以及H3.3的哪些功能可能使快速和高水平的转录。H3.3的氨基末端含有独特的丝氨酸残基，其在“规范”H3.1和H3.2中不存在。我们发现，这个残基，H3.3S31，是磷酸化（H3.3S31ph），在刺激依赖性的方式沿着快速诱导的基因在小鼠巨噬细胞。这种刺激反应基因的选择性标记直接参与组蛋白甲基转移酶SETD2（活性转录机制的一个组成部分）和“eetamine”ZMYND11（延伸辅阻遏物）。我们建议，H3.3的功能在刺激诱导的基因，包括H3.3S31ph，提供优先进入转录装置。我们的研究结果表明，专门的机制，使快速转录涉及组蛋白变体H3.3，其磷酸化，以及招募和喷射的染色质调节。
Complex organisms are able to rapidly induce select genes in response to diverse environmental cues. This regulation occurs in the context of large genomes condensed by histone proteins into chromatin. The macrophage response to pathogen sensing rapidly engages conserved signaling pathways and transcription factors for coordination of inflammatory gene induction. Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription. However, little is known of how chromatin is regulated at rapidly induced genes and what features of H3.3 might enable rapid and high-level transcription. The amino-terminus of H3.3 contains a unique serine residue that is absent in “canonical” H3.1 and H3.2. We find that this residue, H3.3S31, is phosphorylated (H3.3S31ph) in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engages histone methyltransferase SETD2, a component of the active transcription machinery, and “ejects” ZMYND11, an elongation corepressor. We propose that features of H3.3 at stimulation-induced genes, including H3.3S31ph, afford preferential access to the transcription apparatus. Our results indicate dedicated mechanisms enabling rapid transcription involving histone variant H3.3, its phosphorylation, and both recruitment and ejection of chromatin regulators.
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影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
14.8
作者：
Fierz, Beat;Muir, Tom W.
通讯作者：
Muir, Tom W.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
21.3
作者：
Hinchcliffel, Edward H.;Day, Charles A.;Dong, Zigang
通讯作者：
Dong, Zigang
影响因子：
14.9
作者：
Chang FT;Chan FL;R McGhie JD;Udugama M;Mayne L;Collas P;Mann JR;Wong LH
通讯作者：
Wong LH