title: The retinoblastoma binding protein RBP2 is an H3K4 demethylase.
abstract: Changes in histone methylation status regulate chromatin structure and DNA-dependent processes such as transcription. Recent studies indicate that, analogous to other histone modifications, histone methylation is reversible. Retinoblastoma binding protein 2 (RBP2), a nuclear protein implicated in the regulation of transcription and differentiation by the retinoblastoma tumor suppressor protein, contains a JmjC domain recently defined as a histone demethylase signature motif. Here we report that RBP2 is a demethylase that specifically catalyzes demethylation on H3K4, whose methylation is normally associated with transcriptionally active genes. RBP2-/- mouse cells displayed enhanced transcription of certain cytokine genes, which, in the case of SDF1, was associated with increased H3K4 trimethylation. Furthermore, RBP2 specifically demethylated H3K4 in biochemical and cell-based assays. These studies provide mechanistic insights into transcriptional regulation by RBP2 and provide the first example of a mammalian enzyme capable of erasing trimethylated H3K4.
authors.affiliation: Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klose
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tothova
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamane
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: William G
authors.initials: WG
authors.lastname: Kaelin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D018411:Spodoptera / Q000166:cytology; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D006657:Histones; C518460:Rbp2 protein, mouse; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular