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-Structure paper
| タイトル | Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 6815, Year 2024 |
| 掲載日 | 2024年8月9日 |
著者 | Zengyu Shao / Jiuwei Lu / Nelli Khudaverdyan / Jikui Song / ![]() |
| PubMed 要旨 | 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. ...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. |
リンク | Nat Commun / PubMed:39122718 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.76 - 2.88 Å |
| 構造データ | EMDB-44410, PDB-9bap: EMDB-44411, PDB-9baq: EMDB-44415, PDB-9baz: |
| 化合物 | ![]() ChemComp-SAH: ![]() ChemComp-ZN: |
| 由来 |
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キーワード | TRANSFERASE / DNA methyltransferase / Transferase/DNA Binding Protein/DNA / Transferase-DNA Binding Protein-DNA complex |
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neurospora crassa (菌類)
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