H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation

Kee Beom Kim, Hye Ju Son, Sulji Choi, Ja Young Hahm, Hyeonsoo Jung, Hee Jo Baek, Hoon Kook, Yoonsoo Hahn, Hyun Kook, Sang Beom Seo

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Histone H3K9 methyltransferase (HMTase) G9a-mediated transcriptional repression is a major epigenetic silencing mechanism. UHRF1 (ubiquitin-like with PHD and ring finger domains 1) binds to hemimethylated DNA and plays an essential role in the maintenance of DNA methylation. 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 during TPA-mediated leukemia cell differentiation. Using ChIP analysis, we found that UHRF1 was among the transcriptionally silenced genes during leukemia cell differentiation. Using a DNA methylation profiling array, we discovered that the UHRF1 promoter was hypomethylated in samples from leukemia patients, further supporting its overexpression and oncogenic activity. Finally, we showed that G9a regulates UHRF1-mediated H3K23 ubiquitination and proper DNA replication maintenance. Therefore, we propose that H3K9 HMTase G9a is a specific epigenetic regulator of UHRF1.

Original languageEnglish
Pages (from-to)3509-3523
Number of pages15
JournalNucleic Acids Research
Volume43
Issue number7
DOIs
StatePublished - 23 Feb 2015

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