PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-alpha target gene activation by regulating lysine demethylase 1 specificity

EMBO Rep. 2010 Jun;11(6):438-44. doi: 10.1038/embor.2010.62. Epub 2010 May 7.

Abstract

Histone methylation has a key role in oestrogen receptor (ERalpha)-mediated transactivation of genes. Proline glutamic acid and leucine-rich protein 1 (PELP1) is a new proto-oncogene that functions as an ERalpha co-regulator. In this study, we identified histone lysine demethylase, KDM1, as a new PELP1-interacting protein. These proteins, PELP1 and KDM1, were both recruited to ERalpha target genes, and PELP1 depletion affected the dimethyl histone modifications at ERalpha target genes. Dimethyl-modified histones H3K4 and H3K9 are recognized by PELP1, and PELP1 alters the substrate specificity of KDM1 from H3K4 to H3K9. Effective demethylation of dimethyl H3K9 by KDM1 requires a KDM1-ERalpha-PELP1 functional complex. These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERalpha target genes.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Co-Repressor Proteins
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism*
  • Histone Demethylases / metabolism*
  • Histones / metabolism*
  • Humans
  • Methylation / drug effects
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Substrate Specificity / drug effects
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcriptional Activation* / drug effects

Substances

  • Co-Repressor Proteins
  • Estrogen Receptor alpha
  • Histones
  • PELP1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Estradiol
  • Histone Demethylases
  • KDM1A protein, human