Lee Seongyeol, Lee Jieon, Chae Sehyun, Moon Yunwon, Lee Ho-Youl, Park Bongju, Yang Eun Gyeong, Hwang Daehee, Park Hyunsung
Department of Life Science, University of Seoul, Seoul 02504, Republic of Korea.
Department of Chemical Engineering, POSTECH, Pohang 37673, Republic of Korea.
Nucleic Acids Res. 2017 Nov 16;45(20):11643-11657. doi: 10.1093/nar/gkx747.
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.
缺氧通过降低组蛋白去甲基化酶的活性来增加活性和抑制性组蛋白甲基化水平。然而，这种增加如何协同调节缺氧反应基因的诱导或抑制在很大程度上尚不清楚。在这里，我们分析了缺氧条件下人脂肪来源干细胞中的活性和抑制性组蛋白三甲基化（H3K4me3、H3K9me3和H3K27me3），并分析了基因表达谱。我们通过缺氧鉴定了差异表达基因（DEGs）和差异甲基化基因（DMGs），并将DEGs和DMGs聚类为四个主要组。我们发现，每组DEGs主要仅与三种组蛋白三甲基化中的一种类型的改变相关。此外，四组DEGs与不同的转录因子（TFs）及其主要类型的H3K4me3、H3K9me3和H3K27me3的定位模式相关。我们的结果表明，基因表达改变与以不同定位模式为特征的突出的单一类型组蛋白三甲基化以及不同的转录因子集之间的关联有助于特定基因集的调控，这可以作为缺氧条件下基因表达协同表观遗传调控的模型。
