Chromatin remodeling of histone H3 variants underlies epigenetic inheritance of DNA methylation.

Autor:	Lee SC; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Adams DW; W. M. Keck Structural Biology Laboratory, Howard Hughes Medical Institute; Cold Spring Harbor, NY 11724, USA.; Graduate Program in Genetics, Stony Brook University; Stony Brook, NY 11794, USA., Ipsaro JJ; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; W. M. Keck Structural Biology Laboratory, Howard Hughes Medical Institute; Cold Spring Harbor, NY 11724, USA., Cahn J; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Lynn J; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Kim HS; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Berube B; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; Cold Spring Harbor Laboratory School of Biological Sciences; 1 Bungtown Rd, Cold Spring Harbor, NY 11724, USA., Major V; Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh; Edinburgh EH9 3BF, United Kingdom., Calarco JP; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; Cold Spring Harbor Laboratory School of Biological Sciences; 1 Bungtown Rd, Cold Spring Harbor, NY 11724, USA., LeBlanc C; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; Present address: Department of Molecular, Cellular and Developmental Biology, Faculty of Arts and Sciences, Yale University; 260 Whitney Ave., New Haven, CT, 06511, USA., Bhattacharjee S; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Ramu U; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA., Grimanelli D; Institut de Recherche pour le Développement; 911 Avenue Agropolis, 34394 Montpellier, France., Jacob Y; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; Present address: Department of Molecular, Cellular and Developmental Biology, Faculty of Arts and Sciences, Yale University; 260 Whitney Ave., New Haven, CT, 06511, USA., Voigt P; Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh; Edinburgh EH9 3BF, United Kingdom.; Present address: Epigenetics Programme, Babraham Institute; Cambridge CB22 3AT, United Kingdom., Joshua-Tor L; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.; W. M. Keck Structural Biology Laboratory, Howard Hughes Medical Institute; Cold Spring Harbor, NY 11724, USA., Martienssen RA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory; 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 02. Date of Electronic Publication: 2023 Aug 02.
DOI:	10.1101/2023.07.11.548598
Abstrakt:	Epigenetic inheritance refers to the faithful replication of DNA methylation and histone modification independent of DNA sequence. Nucleosomes block access to DNA methyltransferases, unless they are remodeled by DECREASE IN DNA METHYLATION1 (DDM1 Lsh/HELLS ), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 activity results in replacement of the transcriptional histone variant H3.3 for the replicative variant H3.1 during the cell cycle. In ddm1 mutants, DNA methylation can be 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 direct engagement at SHL2 with histone H3.3 at or near variant residues required for assembly, as well as with the deacetylated H4 tail. An N-terminal autoinhibitory domain binds H2A variants to allow remodeling, while a disulfide bond in the helicase domain is essential for activity in vivo and in vitro . We show that differential remodeling of H3 and H2A variants in vitro reflects preferential deposition in vivo . DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1 Dnmt1 . DDM1 localization to the chromosome is blocked by H4K16 acetylation, which accumulates at DDM1 targets in ddm1 mutants, as does the sperm cell specific H3.3 variant MGH3 in pollen, which acts as a placeholder nucleosome in the germline and contributes to epigenetic inheritance.
Databáze:	MEDLINE
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