登録情報 データベース : EMDB / ID : EMD-49676 ダウンロードとリンクタイトル KDM6B-nucleosome structure stabilized by H3K27C-UNC8015 covalent conjugate マップデータcomposite map 詳細 試料複合体 : KDM6B-nucleosome complex stabilized by H3K27C-UNC8015 covalent conjugate複合体 : histones of nucleosomeタンパク質・ペプチド : Histone H3.2タンパク質・ペプチド : Histone H4タンパク質・ペプチド : Histone H2A type 1タンパク質・ペプチド : Histone H2B type 1-C/E/F/G/I複合体 : Widom601 sequence with 20 bp linker DNA at both ends.DNA : DNA (185-MER)DNA : DNA (185-MER)複合体 : Mouse KDM6B C-terminal domainタンパク質・ペプチド : Lysine-specific demethylase 6Bリガンド : FE (III) IONリガンド : ZINC IONリガンド : N-heptanoyl-N-hydroxy-beta-alanine 詳細 キーワード histone H3K27 demethylation / GENE REGULATION / histone / chromatin / epigenetics / GENE REGULATION-DNA complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
[histone H3]-trimethyl-L-lysine27 demethylase / HDMs demethylate histones / histone H3K27me2/H3K27me3 demethylase activity / endothelial cell differentiation / Oxidative Stress Induced Senescence / cardiac muscle cell differentiation / inflammatory response to antigenic stimulus / mesodermal cell differentiation / cell fate commitment / negative regulation of megakaryocyte differentiation ... [histone H3]-trimethyl-L-lysine27 demethylase / HDMs demethylate histones / histone H3K27me2/H3K27me3 demethylase activity / endothelial cell differentiation / Oxidative Stress Induced Senescence / cardiac muscle cell differentiation / inflammatory response to antigenic stimulus / mesodermal cell differentiation / cell fate commitment / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / response to fungicide / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere organization / Interleukin-7 signaling / Inhibition of DNA recombination at telomere / RNA Polymerase I Promoter Opening / Meiotic synapsis / Assembly of the ORC complex at the origin of replication / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / innate immune response in mucosa / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / response to activity / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / hippocampus development / HDACs deacetylate histones / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / HDMs demethylate histones / G2/M DNA damage checkpoint / beta-catenin binding / NoRC negatively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / cellular response to hydrogen peroxide / Transcriptional regulation of granulopoiesis / HCMV Early Events / antimicrobial humoral immune response mediated by antimicrobial peptide / structural constituent of chromatin / UCH proteinases / antibacterial humoral response / nucleosome / heterochromatin formation / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / positive regulation of cold-induced thermogenesis / HATs acetylate histones / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / chromatin organization / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Processing of DNA double-strand break ends / regulation of gene expression / Senescence-Associated Secretory Phenotype (SASP) / Oxidative Stress Induced Senescence / gene expression / Estrogen-dependent gene expression / sequence-specific DNA binding / chromosome, telomeric region / defense response to Gram-positive bacterium / Ub-specific processing proteases / chromatin remodeling / Amyloid fiber formation / protein heterodimerization activity / chromatin binding / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular space / DNA binding / RNA binding 類似検索 - 分子機能 : / : / : / : / Lysine-specific demethylase 6/UTY, C-terminal helical domain / KDM6, GATA-like / JmjC domain, hydroxylase / A domain family that is part of the cupin metalloenzyme superfamily. / JmjC domain / JmjC domain profile. ... : / : / : / : / Lysine-specific demethylase 6/UTY, C-terminal helical domain / KDM6, GATA-like / JmjC domain, hydroxylase / A domain family that is part of the cupin metalloenzyme superfamily. / JmjC domain / JmjC domain profile. / : / Histone H2B signature. / Histone H2A conserved site / Histone H2A signature. / Histone H2B / Histone H2B / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone 2A / Histone H2A / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 domain / Histone-fold 類似検索 - ドメイン・相同性 Histone H2A type 1 / Histone H4 / Histone H2B type 1-C/E/F/G/I / Lysine-specific demethylase 6B / Histone H3.2 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.16 Å 詳細 データ登録者Lin C-C / McGinty RK 資金援助 米国, 3件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35GM133498 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) R35GM139514 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) R01CA010305 米国
引用ジャーナル : Mol Cell / 年 : 2025タイトル : Structural mechanism of H3K27 demethylation and crosstalk with heterochromatin markers.著者 : Chien-Chu Lin / Yani Zhao / Caroline A Foley / Aspen T Hawkins / Lindsey I James / Stephen V Frye / Robert K McGinty / 要旨 : Histone H3 lysine 27 trimethylation (H3K27me3) is a repressive histone modification that is a hallmark of facultative heterochromatin. H3K27me3 is installed by the polycomb repressive complex 2 (PRC2) ... Histone H3 lysine 27 trimethylation (H3K27me3) is a repressive histone modification that is a hallmark of facultative heterochromatin. H3K27me3 is installed by the polycomb repressive complex 2 (PRC2) and removed by KDM6 family Jumonji C (JmjC) domain demethylases. Structural studies have elucidated how PRC2 functions on nucleosomes and its regulation by local histone modification signatures. However, the molecular mechanisms governing H3K27 demethylation to reactivate silenced chromatin remain poorly understood. Here, we report the cryoelectron microscopy (cryo-EM) structure of mouse KDM6B bound to the nucleosome. Our structure shows how KDM6B engages wrapped nucleosomal DNA together with both extranucleosomal DNA linkers to position its catalytic JmjC domain for H3K27 demethylation. KDM6B induces an overlapped linker DNA conformation consistent with function in a compact chromatin environment. We further show that linker histones and H2AK119ub1, both enriched in heterochromatin, antagonize KDM6B function, suggesting that linker histone eviction and H2A deubiquitylation precede H3K27 demethylation during heterochromatin activation. 履歴 登録 2025年3月13日 - ヘッダ(付随情報) 公開 2025年7月23日 - マップ公開 2025年7月23日 - 更新 2025年8月20日 - 現状 2025年8月20日 処理サイト : RCSB / 状態 : 公開
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