- EMDB-44415: CryoEM structure of DIM2-HP1 complex -
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基本情報
登録情報
データベース: EMDB / ID: EMD-44415
タイトル
CryoEM structure of DIM2-HP1 complex
マップデータ
sharpened map
試料
複合体: DIM2-HP1 complex
タンパク質・ペプチド: DNA (cytosine-5-)-methyltransferase
タンパク質・ペプチド: Heterochromatin protein one
リガンド: S-ADENOSYL-L-HOMOCYSTEINE
リガンド: ZINC ION
キーワード
DNA methyltransferase / TRANSFERASE
機能・相同性
機能・相同性情報
regulation of biosynthetic process / DNA (cytosine-5-)-methyltransferase / DNA (cytosine-5-)-methyltransferase activity / negative regulation of gene expression via chromosomal CpG island methylation / heterochromatin / methylation / chromatin remodeling / chromatin binding / DNA binding / nucleus 類似検索 - 分子機能
: / Domain of unknown function (DUF7893) / Chromo shadow domain / Chromo shadow domain / Chromo Shadow Domain / : / : / Chromo domain, conserved site / DNA methylase, C-5 cytosine-specific, active site / C-5 cytosine-specific DNA methylases active site. ...: / Domain of unknown function (DUF7893) / Chromo shadow domain / Chromo shadow domain / Chromo Shadow Domain / : / : / Chromo domain, conserved site / DNA methylase, C-5 cytosine-specific, active site / C-5 cytosine-specific DNA methylases active site. / Chromo domain signature. / C-5 cytosine-specific DNA methylase (Dnmt) domain profile. / C-5 cytosine methyltransferase / C-5 cytosine-specific DNA methylase / Chromo domain / Chromo (CHRromatin Organisation MOdifier) domain / Chromo and chromo shadow domain profile. / Bromo adjacent homology (BAH) domain / Bromo adjacent homology (BAH) domain superfamily / BAH domain profile. / Chromo/chromo shadow domain / Chromatin organization modifier domain / Chromo-like domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily 類似検索 - ドメイン・相同性
Heterochromatin protein one / DNA (cytosine-5-)-methyltransferase 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
米国
引用
ジャーナル: Nat Commun / 年: 2024 タイトル: Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation. 著者: Zengyu Shao / Jiuwei Lu / Nelli Khudaverdyan / Jikui Song / 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.