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

Weijun Feng, Masato Yonezawa, Jing Ye, Thomas Jenuwein, Ingrid Grummt

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)445-450
Number of pages6
JournalNature Structural and Molecular Biology
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2010

Fingerprint

rRNA Genes
Fingers
Ribosomal DNA
Proteins
Methylation
Lysine
Cleft Lip
Methyltransferases
Cleft Palate
Intellectual Disability
Histones
Transcriptional Activation
RNA Polymerase I
Point Mutation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. / Feng, Weijun; Yonezawa, Masato; Ye, Jing; Jenuwein, Thomas; Grummt, Ingrid.

In: Nature Structural and Molecular Biology, Vol. 17, No. 4, 01.04.2010, p. 445-450.

Research output: Contribution to journalArticle

Feng, Weijun ; Yonezawa, Masato ; Ye, Jing ; Jenuwein, Thomas ; Grummt, Ingrid. / PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 4. pp. 445-450.
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