Histone H3.3 phosphorylation amplifies stimulation-induced transcription
| Autor: | Anja Armache, Tanja Arslan, Thais Klevorn, Andrew W Daman, Arjun Ravishankar, Dughan J. Ahimovic, Tanya Panchenko, Steven Z. Josefowicz, Joel Hrit, Benjamin A. Garcia, Shu Lin, Karim-Jean Armache, Yuan Yue, Sandra B. Hake, Erica Korb, C. David Allis, Haitao Li, Jin Q. Cheong, Alexia Martínez de Paz, Ceyda Durmaz, Scott B. Rothbart, Miao Wang, Shuang Yang, Lexi E. Robbins, Samuel Thudium |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Models Molecular Transcription Genetic Cell Cycle Proteins Methylation Article Histones Mice 03 medical and health sciences Histone H3 0302 clinical medicine Animals Humans Epigenetics Phosphorylation Transcription factor Cells Cultured 030304 developmental biology 0303 health sciences Multidisciplinary biology Chemistry Macrophages Histone-Lysine N-Methyltransferase I-kappa B Kinase Up-Regulation Chromatin Cell biology DNA-Binding Proteins Histone phosphorylation Histone 030220 oncology & carcinogenesis Histone methyltransferase biology.protein Co-Repressor Proteins Corepressor |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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 genes1–3. Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription4–7. 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 ZMYND118,9. 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. |
| Databáze: | OpenAIRE |
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