title: H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation.
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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Kee-Beom
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Hye-Ju
authors.initials: HJ
authors.lastname: Son
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Sulji
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Hahm
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Hyeonsoo
authors.initials: H
authors.lastname: Jung
authors.affiliation: Environmental Health Center for Childhood Leukemia and Cancer, Department of Pediatrics, Chonnam National University Hwasun Hospital, Hwasun 519-809.
authors.forename: Hee Jo
authors.initials: HJ
authors.lastname: Baek
authors.affiliation: Environmental Health Center for Childhood Leukemia and Cancer, Department of Pediatrics, Chonnam National University Hwasun Hospital, Hwasun 519-809.
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756.
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Hahn
authors.affiliation: Medical Research Center for Gene Regulation and Department of Pharmacology, Chonnam National University, Gwangju 501-746, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756 sangbs@cau.ac.kr.
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D015254:DNA Modification Methylases / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D015254:DNA Modification Methylases; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases