生物
组蛋白H3
组蛋白甲基化
核小体
表观遗传学
遗传学
组蛋白密码
DNA甲基化
组蛋白
细胞生物学
染色质
组蛋白甲基转移酶
染色质重塑
DNA
基因
基因表达
作者
Seung Cho Lee,Dexter W. Adams,Jonathan J. Ipsaro,Jonathan Cahn,Jason Lynn,Hyun Soo Kim,Benjamin Berube,Viktoria Major,Joseph P. Calarco,Chantal LeBlanc,Maike Sander,Umamaheswari Ramu,Daniel Grimanelli,Yannick Jacob,Philipp Voigt,Leemor Joshua‐Tor,Robert A. Martienssen
出处
期刊:Cell
[Elsevier]
日期:2023-09-01
卷期号:186 (19): 4100-4116.e15
被引量:11
标识
DOI:10.1016/j.cell.2023.08.001
摘要
Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1LSH/HELLS), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.1. In ddm1 mutants, DNA methylation is partly restored by loss of the H3.3 chaperone HIRA, while the H3.1 chaperone CAF-1 becomes essential. The single-particle cryo-EM structure at 3.2 Å of DDM1 with a variant nucleosome reveals engagement with histone H3.3 near residues required for assembly and with the unmodified H4 tail. An N-terminal autoinhibitory domain inhibits activity, while a disulfide bond in the helicase domain supports activity. DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1Dnmt1, but is blocked by H4K16 acetylation. The male germline H3.3 variant MGH3/HTR10 is resistant to remodeling by DDM1 and acts as a placeholder nucleosome in sperm cells for epigenetic inheritance.
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