GSE63149
H3K9 methyltransferase G9a negatively regulates UHRF1 transdcription during leukemia cell differentiation.
Posttranslational modifications of histone N-terminal tails influence the status of chromatin and eventually control the transcriptional outcome of a particular gene. As a histone H3K9 methyltransferase (HMTase) in higher eukaryotes, G9a-mediated transcriptional repression is the major epigenetic silencing machinery. UHRF1 (ubiquitin-like with PHD and ring finger domains I) binds to hemi-methylated DNA and plays essential role in maintenance of DNA methylation by recruiting DNMT1. Here, we provide evidence that UHRF1 is transcriptionally downregulated by H3K9 HMTase G9a. We found that increased expression of G9a along with transcription factor YY1 specifically represses UHRF1 transcription. We uncovered showed that G9a regulates UHRF1-mediated H3K23 ubiquitylation and proper DNA replication maintenance by FACS analysis and propose that H3K9 HMTase G9a is a specific epigenetic regulator of UHRF1. Overall design: Identification of Histone 3 acetylation (Acetyl-H3) marks, RNA polymerase II (PolII) binding sites, Histone deacetylase 2 (HDAC2), Histone 3 lysine 27 trimethylation (H3K27-me3) marks, and Histone 2A lysine 119 ubiquitination (H2AK119-ub) marks in HL-60 cells treated with 32 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) or solvent control.