A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation

Mol Cell. 2010 Apr 23;38(2):165-78. doi: 10.1016/j.molcel.2010.03.002. Epub 2010 Mar 25.


X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionally link the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionally linked in pathways, causing the complex phenotypes observed in patients developing MR.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Male
  • Mental Retardation, X-Linked / genetics*
  • Methylation
  • Molecular Sequence Data
  • Mutation
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Recombinant Proteins
  • Transcription Factors
  • ZNF711 protein, human
  • Histone Demethylases
  • PHF8 protein, human

Associated data

  • GENBANK/GSE20673