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

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

doi:10.1038/nsmb.1778

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

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Jenuwein, Thomas
Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Feng, W., Yonezawa, M., Ye, J., Jenuwein, T., & Grummt, I. (2010). PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. Nature Structural and Molecular Biology, 17, 445-450. doi:10.1038/nsmb.1778.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-8E95-A

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.