Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation

Nat Cell Biol. 2008 Jan;10(1):53-60. doi: 10.1038/ncb1668. Epub 2007 Dec 9.


Posttranslational modifications of histones such as methylation, acetylation and phosphorylation regulate chromatin structure and gene expression. Here we show that protein-kinase-C-related kinase 1 (PRK1) phosphorylates histone H3 at threonine 11 (H3T11) upon ligand-dependent recruitment to androgen receptor target genes. PRK1 is pivotal to androgen receptor function because PRK1 knockdown or inhibition impedes androgen receptor-dependent transcription. Blocking PRK1 function abrogates androgen-induced H3T11 phosphorylation and inhibits androgen-induced demethylation of histone H3. Moreover, serine-5-phosphorylated RNA polymerase II is no longer observed at androgen receptor target promoters. Phosphorylation of H3T11 by PRK1 accelerates demethylation by the Jumonji C (JmjC)-domain-containing protein JMJD2C. Thus, phosphorylation of H3T11 by PRK1 establishes a novel chromatin mark for gene activation, identifying PRK1 as a gatekeeper of androgen receptor-dependent transcription. Importantly, levels of PRK1 and phosphorylated H3T11 correlate with Gleason scores of prostate carcinomas. Finally, inhibition of PRK1 blocks proliferation of androgen receptor-induced tumour cell proliferation, making PRK1 a promising therapeutic target.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation*
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Phosphorylation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Threonine / metabolism*
  • Tissue Array Analysis
  • Transcription, Genetic
  • Transcriptional Activation


  • Chromatin
  • Histones
  • Receptors, Androgen
  • Threonine
  • protein kinase N
  • Protein Kinase C