Open AccessH3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation
Author(s) -
KeeBeom Kim,
Hye-Ju Son,
Sulji Choi,
Ja Young Hahm,
Hyeonsoo Jung,
Hee Jo Baek,
Hoon Kook,
Yoonsoo Hahn,
Hyun Kook,
SangBeom Seo
Publication year - 2015
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkv183
Subject(s) - biology , dna methylation , epigenetics , epigenetics of physical exercise , dna methyltransferase , transcription factor , polycomb group proteins , histone methyltransferase , methyltransferase , microbiology and biotechnology , genetics , methylation , dna , repressor , gene , gene expression
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.
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