Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia.
Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia.
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DOI：
10.1093/nar/gkx747
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发表时间：
2017-11-16
影响因子：
14.9
通讯作者：
Park H
中科院分区：
文献类型：
--
作者：
Lee S;Lee J;Chae S;Moon Y;Lee HY;Park B;Yang EG;Hwang D;Park H
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，这种增加如何协调调节缺氧反应基因的诱导或抑制在很大程度上是未知的。在这里，我们分析了活性和抑制性组蛋白三甲基化（H3K4me3，H3K9me3和H3K27me3），并分析了缺氧条件下人脂肪细胞源性干细胞的基因表达谱。我们发现差异表达基因（DEG）和差异甲基化基因（DMG）的缺氧和聚类的DEG和DMG分为四个主要群体。我们发现，每组DEG主要与三种组蛋白三甲基化中仅一种类型的改变相关。此外，四组DEG与不同的TF及其优势类型H3K4me3，H3K9me3和H3K27me3的定位模式相关。我们的研究结果表明，改变基因表达与突出的单一类型的组蛋白三甲基化，其特征在于不同的定位模式和不同的TF集的协会有助于调节特定的基因集，这可以作为一个模型，协调缺氧下的基因表达的表观遗传调控。
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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