7ux9
Arabidopsis DDM1 bound to nucleosome (H2A.W, H2B, H3.3, H4, with 147 bp DNA)Arabidopsis DDM1 bound to nucleosome (H2A.W, H2B, H3.3, H4, with 147 bp DNA)
Structural highlights
FunctionH2A7_ARATH Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Publication Abstract from PubMedNucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1(LSH)((/)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 A 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 MET1(Dnmt1), 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. Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.,Lee SC, Adams DW, Ipsaro JJ, Cahn J, Lynn J, Kim HS, Berube B, Major V, Calarco JP, LeBlanc C, Bhattacharjee S, Ramu U, Grimanelli D, Jacob Y, Voigt P, Joshua-Tor L, Martienssen RA Cell. 2023 Sep 14;186(19):4100-4116.e15. doi: 10.1016/j.cell.2023.08.001. Epub , 2023 Aug 28. PMID:37643610[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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