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TitleMulti-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 6815, Year 2024
Publish dateAug 9, 2024
AuthorsZengyu Shao / Jiuwei Lu / Nelli Khudaverdyan / Jikui Song /
PubMed AbstractFunctional crosstalk between DNA methylation, histone H3 lysine-9 trimethylation (H3K9me3) and heterochromatin protein 1 (HP1) is essential for proper heterochromatin assembly and genome stability. ...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.
External linksNat Commun / PubMed:39122718 / PubMed Central
MethodsEM (single particle)
Resolution2.76 - 2.88 Å
Structure data

44410

9bap

EMDB-44410, PDB-9bap:
CryoEM structure of Apo-DIM2
Method: EM (single particle) / Resolution: 2.88 Å

44411

9baq

EMDB-44411, PDB-9baq:
CryoEM structure of DIM2-HP1-H3K9me3-DNA complex
Method: EM (single particle) / Resolution: 2.79 Å

44415

9baz

EMDB-44415, PDB-9baz:
CryoEM structure of DIM2-HP1 complex
Method: EM (single particle) / Resolution: 2.76 Å

Chemicals

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE

ChemComp-ZN:
Unknown entry

Source
  • neurospora crassa (fungus)
KeywordsTRANSFERASE / DNA methyltransferase / Transferase/DNA Binding Protein/DNA / Transferase-DNA Binding Protein-DNA complex

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