Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia
 Authors and Affiliations
 Authors and Affiliations
Seongyeol Lee1,†, Jieon Lee2,†, Sehyun Chae3,†, Yunwon Moon1,†, Ho-Youl Lee1, Bongju Park1, Eun Gyeong Yang4, Daehee Hwang2,3,* and Hyunsung Park1,*
1Department of Life Science, University of Seoul, Seoul 02504, Republic of Korea, 2Department of Chemical Engineering, POSTECH, Pohang 37673, Republic of Korea, 3Department of New Biology and Center for Plant Aging Research, Institute of Basic Science, DGIST, Daegu 42988, Republic of Korea and 4Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea †These authors contributed equally to this work as first authors.
*To whom correspondence should be addressed. Correspondence may also be addressed to Daehee Hwang.
Abstract Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia.
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