6J9J

crystal structure of SESTD2 in complex with H3.3S31phK36M peptide

6J9J の概要

• エントリーDOI: 10.2210/pdb6j9j/pdb
• 分子名称: Histone-lysine N-methyltransferase SETD2, H3.3S31phK36M(29-42), ZINC ION, ... (6 entities in total)
• 機能のキーワード: methyltransferase, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32149.59

構造登録者

Yang, S.,Li, H.T. (登録日: 2019-01-23, 公開日: 2020-02-26, 最終更新日: 2024-10-23)

主引用文献

Armache, A.,Yang, S.,Martinez de Paz, A.,Robbins, L.E.,Durmaz, C.,Cheong, J.Q.,Ravishankar, A.,Daman, A.W.,Ahimovic, D.J.,Klevorn, T.,Yue, Y.,Arslan, T.,Lin, S.,Panchenko, T.,Hrit, J.,Wang, M.,Thudium, S.,Garcia, B.A.,Korb, E.,Armache, K.J.,Rothbart, S.B.,Hake, S.B.,Allis, C.D.,Li, H.,Josefowicz, S.Z.
Histone H3.3 phosphorylation amplifies stimulation-induced transcription.
Nature, 583:852-857, 2020

PubMed Abstract: 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. Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription. 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. 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.

PubMed: 32699416
DOI: 10.1038/s41586-020-2533-0

実験手法

X-RAY DIFFRACTION (1.78 Å)