Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation

Mol Cell. 2008 Aug 22;31(4):520-30. doi: 10.1016/j.molcel.2008.08.004.


Retinoblastoma protein (pRB) mediates cell-cycle withdrawal and differentiation by interacting with a variety of proteins. RB-Binding Protein 2 (RBP2) has been shown to be a key effector. We sought to determine transcriptional regulation by RBP2 genome-wide by using location analysis and gene expression profiling experiments. We describe that RBP2 shows high correlation with the presence of H3K4me3 and its target genes are separated into two functionally distinct classes: differentiation-independent and differentiation-dependent genes. The former class is enriched by genes that encode mitochondrial proteins, while the latter is represented by cell-cycle genes. We demonstrate the role of RBP2 in mitochondrial biogenesis, which involves regulation of H3K4me3-modified nucleosomes. Analysis of expression changes upon RBP2 depletion depicted genes with a signature of differentiation control, analogous to the changes seen upon reintroduction of pRB. We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Differentiation / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human / genetics*
  • Genomics
  • Histones / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lysine / metabolism*
  • Methylation
  • Mitochondria / enzymology
  • Models, Biological
  • Nucleosomes / enzymology
  • Oxidoreductases, N-Demethylating / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Repressor Proteins / metabolism
  • Retinoblastoma-Binding Protein 2
  • Sequence Analysis, DNA
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Tumor Suppressor Proteins / metabolism*


  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nucleosomes
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • KDM5A protein, human
  • Retinoblastoma-Binding Protein 2
  • Oxidoreductases, N-Demethylating
  • Lysine