PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation

Nat Struct Mol Biol. 2010 Apr;17(4):445-50. doi: 10.1038/nsmb.1778. Epub 2010 Mar 7.


Histone lysine methylation is dynamically regulated by lysine methyltransferases and lysine demethylases. Here we show that PHD finger protein 8 (PHF8), a protein containing a PHD finger and a Jumonji C (JmjC) domain, is associated with hypomethylated rRNA genes (rDNA). PHF8 interacts with the RNA polymerase I transcription machinery and with WD repeat-containing protein 5 (WDR5)-containing H3K4 methyltransferase complexes. PHF8 exerts a positive effect on rDNA transcription, with transcriptional activation requiring both the JmjC domain and the PHD finger. PHF8 demethylates H3K9me1/2, and its catalytic activity is stimulated by adjacent H3K4me3. A point mutation within the JmjC domain that is linked to mental retardation with cleft lip and palate (XLMR-CL/P) abolishes demethylase activity and transcriptional activation. Though further work is needed to unravel the contribution of PHF8 activity to mental retardation and cleft lip/palate, our results reveal a functional interplay between H3K4 methylation and H3K9me1/2 demethylation, linking dynamic histone methylation to rDNA transcription and neural disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Histone Demethylases
  • Histones / metabolism*
  • Humans
  • Methylation
  • Protein Binding
  • RNA, Ribosomal / genetics*
  • Transcription Factors / physiology*
  • Transcriptional Activation / physiology*


  • Histones
  • RNA, Ribosomal
  • Transcription Factors
  • Histone Demethylases
  • PHF8 protein, human