The retinoblastoma binding protein RBP2 is an H3K4 demethylase.
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.
Pubmed ID: 17320163 RIS Download
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