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

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

Weijun Feng  1 , Masato Yonezawa, Jing Ye, Thomas Jenuwein, Ingrid Grummt
Affiliations

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

Weijun Feng et al. Nat Struct Mol Biol. 2010 Apr.

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.

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