6j9j
crystal structure of SESTD2 in complex with H3.3S31phK36M peptide
Structural highlights
FunctionSETD2_HUMAN Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.[1] Publication Abstract from PubMedComplex 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. Histone H3.3 phosphorylation amplifies stimulation-induced transcription.,Armache A, Yang S, Martinez 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 Nature. 2020 Jul;583(7818):852-857. doi: 10.1038/s41586-020-2533-0. Epub 2020 Jul, 22. PMID:32699416[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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