PHD Finger Protein 2 (PHF2) Represses Ribosomal RNA Gene Transcription by Antagonizing PHF Finger Protein 8 (PHF8) and Recruiting Methyltransferase SUV39H1

Abstract

Regulation of rDNA transcription is central to cell growth and proliferation. PHF2 and PHF8 belong to a subfamily of histone demethylases that also possess a PHD domain-dependent di-/trimethylated histone 3 lysine 4 (H3K4me2/3) binding activity and are known to be enriched in the nucleolus. In this study, we show that, unlike PHF8 that activates rDNA transcription, PHF2 inhibits rDNA transcription. Depletion of PHF2 by RNA interference increases and overexpression of PHF2 decreases rDNA transcription, respectively, whereas simultaneous depletion of PHF8 and PHF2 restores the level of rDNA transcription. The inhibition of rDNA transcription by PHF2 depends on its H3K4me2/3 binding activity that is also required for PHF2 association with the promoter of rDNA genes but not its demethylase activity. We provide evidence that PHF2 is likely to repress rDNA transcription by competing with PHF8 for binding of rDNA promoter and by recruiting H3K9me2/3 methyltransferase SUV39H1. We also provide evidence that, whereas PHF8 promotes, PHF2 represses the transcriptional activity of RARα, Oct4, and KLF4 and a few PHF8 target genes tested. Taken together, our study demonstrates a repressive role for PHF2 in transcription by RNA polymerase I and II.