title: Acidic domains differentially read histone H3 lysine 4 methylation status and are widely present in chromatin-associated proteins.
abstract: Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin (NPM1), pp32, SET/TAF1β, nucleolin (NCL) and upstream binding factor (UBF) are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4me1 and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2. Furthermore, we demonstrate that the acidic domain with sufficient length alone is capable of binding H3K4me2 in vitro and in vivo. NPM1, NCL and UBF require their acidic domains for association with and transcriptional activation of rDNA genes. Interestingly, by defining acidic domain as a sequence with at least 20 acidic residues in 50 continuous amino acids, we identified 655 acidic domain-containing protein coding genes in the human genome and Gene Ontology (GO) analysis showed that many of the acidic domain proteins have chromatin-related functions. Our data suggest that acidic domain is a novel histone binding motif that can differentially read the status of H3K4 methylation and is broadly present in chromatin-associated proteins.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS USR 3010, Laboratoire Joliot-Curie, Lyon, 69364, France.
authors.forename: Rong
authors.initials: R
authors.lastname: Cong
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Tieliu
authors.initials: T
authors.lastname: Shi
authors.affiliation: Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS USR 3010, Laboratoire Joliot-Curie, Lyon, 69364, France.|Université de Lyon, Centre de Recherche en Cancérologie de Lyon, Cancer Cell Plasticity Department, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Lyon, France
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouvet
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. jmweng@bio.ecnu.edu.cn.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. jmweng@bio.ecnu.edu.cn.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Wong
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. xxdu@bio.ecnu.edu.cn.
authors.forename: James X
authors.initials: JX
authors.lastname: Du
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000097796:Nucleolin
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D035463:Pol1 Transcription Initiation Complex Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000097796:Nucleolin; C087425:ANP32A protein, human; C000716967:NPM1 protein, human; C513473:SET protein, human; C063844:transcription factor UBF
keywords: H3K4me1; H3K4me2; H3K4me3; acidic domain; chromatin; histone code; histone methylation; transcription