The Retinoblastoma Binding Protein Rbp2 is an H3k4 Demethylase.
From: Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell
- Publish Date: Mar 2007
- ISSN: 0092-8674
- Volume: 128
- Issue: 5
- Pages: 889-900
- Medium: Print
- Language: English
- Citation (JAMA): Klose Robert J, Yan Qin, Tothova Zuzana, et al. The Retinoblastoma Binding Protein Rbp2 is an H3k4 Demethylase.. Cell Mar 2007;128:889-900
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.
Mesh Headings (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
Check for Full Text / PubMed Unique Identifier (PMID): 17320163
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