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Histone H3.3 phosphorylation amplifies stimulation-induced transcription
Nature ( IF 64.8 ) Pub Date : 2020-07-22 , DOI: 10.1038/s41586-020-2533-0
Anja Armache 1, 2 , Shuang Yang 3 , Alexia Martínez de Paz 1 , Lexi E Robbins 1 , Ceyda Durmaz 1 , Jin Q Cheong 1 , Arjun Ravishankar 1 , Andrew W Daman 1 , Dughan J Ahimovic 1 , Thaís Klevorn 1 , Yuan Yue 3 , Tanja Arslan 4 , Shu Lin 5 , Tanya Panchenko 2, 6 , Joel Hrit 7 , Miao Wang 8 , Samuel Thudium 9 , Benjamin A Garcia 4 , Erica Korb 9 , Karim-Jean Armache 8 , Scott B Rothbart 7 , Sandra B Hake 4, 10 , C David Allis 2 , Haitao Li 3 , Steven Z Josefowicz 1
Affiliation  

Complex organisms can 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 sensing of pathogens by macrophages engages conserved signalling pathways and transcription factors to coordinate the induction of inflammatory genes 1 – 3 . Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription 4 – 7 . However, how chromatin is regulated at induced genes, and what features of H3.3 might enable rapid and high-level transcription, are unknown. The amino terminus of H3.3 contains a unique serine residue (Ser31) that is absent in ‘canonical’ H3.1 and H3.2. Here we show 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 the histone methyltransferase SETD2, a component of the active transcription machinery, and ‘ejects’ the elongation corepressor ZMYND11 8 , 9 . We propose that features of H3.3 at stimulation-induced genes, including H3.3S31ph, provide preferential access to the transcription apparatus. Our results indicate dedicated mechanisms that enable rapid transcription involving the histone variant H3.3, its phosphorylation, and both the recruitment and the ejection of chromatin regulators. The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.

中文翻译:

组蛋白 H3.3 磷酸化放大刺激诱导的转录

复杂的生物可以快速诱导选择基因以响应不同的环境线索。这种调节发生在由组蛋白浓缩成染色质的大型基因组的背景下。巨噬细胞对病原体的感知利用保守的信号通路和转录因子来协调炎症基因 1-3 的诱导。组蛋白 H3.3(祖先组蛋白 H3 变体)的丰富整合是动态调节染色质和转录 4-7 的一般特征。然而,染色质是如何在诱导基因上被调控的,以及 H3.3 的哪些特征可能实现快速和高水平的转录,这些都是未知的。H3.3 的氨基末端包含一个独特的丝氨酸残基 (Ser31),“规范”H3.1 和 H3.2 中不存在该残基。在这里,我们表明这个残基 H3.3S31 是磷酸化的(H3.3S31)。3S31ph)以刺激依赖性方式沿着小鼠巨噬细胞中快速诱导的基因。这种刺激反应基因的选择性标记直接与组蛋白甲基转移酶 SETD2(活性转录机制的一个组成部分)结合,并“排出”延伸辅阻遏物 ZMYND11 8 、 9 。我们建议 H3.3 在刺激诱导基因上的特征,包括 H3.3S31ph,提供对转录装置的优先访问。我们的结果表明了能够实现快速转录的专用机制,涉及组蛋白变体 H3.3、其磷酸化以及染色质调节剂的募集和排出。组蛋白变体 H3.3 在诱导基因中的 S​​er31 位点被磷酸化,这种选择性标记刺激组蛋白甲基转移酶 SETD2 并排出 ZMYND11 阻遏物,
更新日期:2020-07-22
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