| 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. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: |
controlled study; unclassified drug; methylation; nonhuman; chemical analysis; protein domain; protein function; protein motif; animal cell; mouse; mammalia; animals; mice; gene; nuclear protein; embryo; animal experiment; cell differentiation; transcription, genetic; enzyme activity; cell assay; structure activity relation; mice, inbred c57bl; mice, transgenic; mice, inbred strains; gene expression regulation; cytokine; cytokines; dna; protein processing; transcription regulation; oligonucleotide array sequence analysis; histone h3; fibroblasts; spodoptera; mutagenesis, site-directed; protein structure, tertiary; tumor suppressor protein; histones; nih 3t3 cells; lysine; enzyme mechanism; dna transcription; protein methylation; protein modification; null allele; chromatin structure; demethylation; retinoblastoma binding protein 2; sdf1 gene; retinol-binding proteins
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