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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.

Original publication

DOI

10.1016/j.cell.2007.02.013

Type

Journal article

Journal

Cell

Publication Date

09/03/2007

Volume

128

Pages

889 - 900

Keywords

Animals, Cytokines, Embryo, Mammalian, Embryo, Nonmammalian, Female, Fibroblasts, Gene Expression Regulation, Histones, 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, Retinol-Binding Proteins, Cellular, Spodoptera, Transcription, Genetic