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Nucleic Acids Res. 2017 Nov 16;45(20):11643-11657. doi: 10.1093/nar/gkx747.

Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia.

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Department of Life Science, University of Seoul, Seoul 02504, Republic of Korea.
Department of Chemical Engineering, POSTECH, Pohang 37673, Republic of Korea.
Department of New Biology and Center for Plant Aging Research, Institute of Basic Science, DGIST, Daegu 42988, Republic of Korea.
Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.


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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