Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 Aug 2024
09 Aug 2024
Historique:
received:
12
04
2024
accepted:
01
08
2024
medline:
10
8
2024
pubmed:
10
8
2024
entrez:
9
8
2024
Statut:
epublish
Résumé
Functional crosstalk between DNA methylation, histone H3 lysine-9 trimethylation (H3K9me3) and heterochromatin protein 1 (HP1) is essential for proper heterochromatin assembly and genome stability. However, how repressive chromatin cues guide DNA methyltransferases for region-specific DNA methylation remains largely unknown. Here, we report structure-function characterizations of DNA methyltransferase Defective-In-Methylation-2 (DIM2) in Neurospora. The DNA methylation activity of DIM2 requires the presence of both H3K9me3 and HP1. Our structural study reveals a bipartite DIM2-HP1 interaction, leading to a disorder-to-order transition of the DIM2 target-recognition domain that is essential for substrate binding. Furthermore, the structure of DIM2-HP1-H3K9me3-DNA complex reveals a substrate-binding mechanism distinct from that for its mammalian orthologue DNMT1. In addition, the dual recognition of H3K9me3 peptide by the DIM2 RFTS and BAH1 domains allosterically impacts the DIM2-substrate binding, thereby controlling DIM2-mediated DNA methylation. Together, this study uncovers how multiple heterochromatin factors coordinately orchestrate an activity-switching mechanism for region-specific DNA methylation.
Identifiants
pubmed: 39122718
doi: 10.1038/s41467-024-51246-4
pii: 10.1038/s41467-024-51246-4
doi:
Substances chimiques
Heterochromatin
0
Chromosomal Proteins, Non-Histone
0
Histones
0
Chromobox Protein Homolog 5
107283-02-3
Fungal Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6815Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R35GM119721
Informations de copyright
© 2024. The Author(s).
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