Journal of Stem Cell Research & Therapy

H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during leukemia cell differentiation

4^th International Conference and Exhibition on Cell & Gene Therapy

August 10-12, 2015 London, UK

Sang-Beom Seo1, Kee-Beom Kim1, Hye-Ju Son1, Sulji Choi1, Ja Young Hahm1, Hyeonsoo Jung1, Hee Jo Baek2, Hoon Kook2, Yoonsoo Hahn1 and Hyun Kook3

Posters-Accepted Abstracts: J Stem Cell Res Ther

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.

Biography :

Sang-Beom Seo has completed his PhD from State University of New York/Binghamton and Post-doctoral studies from Pennsylvania University School of Medicine.
He is the Chairperson of Department of Life Science, Chung-Ang University in Seoul, Korea. He has published more than 65 papers in reputed journals.