H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation

Nucleic Acids Research
Kee-Beom KimSang-Beom Seo

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.

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Citations

May 28, 2016·Nucleic Acids Research·Vinay Kumar RaoReshma Taneja
Jan 21, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Vinay Kumar RaoReshma Taneja
Jul 13, 2017·Epigenomics·Amir Hosseini, Saverio Minucci
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao YinHongjuan Cui
Feb 22, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Harsimran Sidhu, Neena Capalash
Mar 15, 2019·Cell Death & Disease·Shruti SrinivasanReshma Taneja
Dec 12, 2018·Nucleic Acids Research·Yun-Cheol ChaeSang-Beom Seo
Dec 6, 2019·Journal of Assisted Reproduction and Genetics·Weiqiang ZhuRunsheng Li
Dec 30, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Nirmalya Saha, Andrew G Muntean
Jun 10, 2021·European Journal of Medicinal Chemistry·Ying-Chao DuanYuan-Yuan Guan

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Datasets Mentioned

BETA
GSE61610
GSE61611

Methods Mentioned

BETA
ubiquitination
PCR
histone acetylation
FCS
immunoprecipitation
fluorescence-activated cell sorting
transfection
ChIP
FACS
ChIP-seq

Software Mentioned

Illumina GenomeStudio
BeadScan
R
Illumina
Excel
BD Accuri C6
Quantity One

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