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	Robert J Klose, Qin Yan, Zuzana Tothova, Kenichi Yamane, Hediye Erdjument-Bromage, Paul Tempst, D Gary Gilliland, Yi Zhang, William G Kaelin Jr
Journal	Cell (Cell) Vol. 128 Issue 5 Pg. 889-900 (Mar 09 2007) ISSN: 0092-8674 [Print] United States
PMID	17320163 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cytokines Histones Rbp2 protein, mouse Retinol-Binding Proteins Retinol-Binding Proteins, Cellular
Topics	Animals Cytokines (genetics) Embryo, Mammalian (cytology) Embryo, Nonmammalian Female Fibroblasts (metabolism) Gene Expression Regulation Histones (metabolism) Male Methylation Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Transgenic Mutagenesis, Site-Directed NIH 3T3 Cells Oligonucleotide Array Sequence Analysis Protein Structure, Tertiary Retinol-Binding Proteins (chemistry, genetics, metabolism) Retinol-Binding Proteins, Cellular Spodoptera (cytology) Transcription, Genetic

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