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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


  • Klose RJ
  • Yan Q
  • Tothova Z
  • Yamane K
  • Erdjument-Bromage H
  • Tempst P
  • Gilliland DG
  • Zhang Y
  • Kaelin WG



Publication Data

March 9, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 076120
  • Agency: NIGMS NIH HHS, Id: GM 68804

Mesh Terms

  • 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