The retinoblastoma binding protein RBP2 is an H3K4 demethylase.

Journal article

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: Klose, R; Yan, Q; Tothova, Z; Yamane, K; Erdjument-Bromage, H

• Publication status: Published
• Journal: Cell
• Volume: 128
• Issue: 5
• Pages: 889-900
• Publication date: 2007-03-01
• DOI: 10.1016/j.cell.2007.02.013
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: Histones; Spodoptera; Male; Retinol-Binding Proteins, Cellular; Female; Mice, Transgenic; Gene Expression Regulation; Embryo, Mammalian; Protein Structure, Tertiary; Mice, Inbred C57BL; Mice, Inbred Strains; Methylation; Retinol-Binding Proteins; Oligonucleotide Array Sequence Analysis; Fibroblasts; Transcription, Genetic; Mice; Embryo, Nonmammalian; Mutagenesis, Site-Directed; Cytokines; NIH 3T3 Cells; Animals