Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation [bisulfite-seq]
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ABSTRACT: Epigenetic inheritance refers to the faithful replication of DNA and histone modification independent of DNA sequence. Nucleosomes block access to DNA methyltransferase during S phase, unless they are remodeled by Decrease in DNA methylation 1 (DDM1Lsh/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. Inddm1mutants, 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 di-sulphide bond in the helicase domain is essential for activity in vivo and in vitro. 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 MET1Dnmt1. 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 and contributes to epigenetic inheritance.
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE231564 | GEO | 2023/11/27
REPOSITORIES: GEO
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