脱甲基酶
H3K4me3
组蛋白甲基化
组蛋白
染色质
表观遗传学
生物
染色质重塑
表观遗传学
细胞生物学
DNA甲基化
组蛋白H1
组蛋白H3
生物化学
组蛋白甲基转移酶
染色质免疫沉淀
甲基化
组蛋白H2A
表观基因组
组蛋白密码
分子生物学
EZH2型
基因表达
基因
发起人
核小体
作者
Michael Batie,Julianty Frost,Mark Frost,James W. Wilson,Pietà Schofield,Sónia Rocha
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2019-03-15
卷期号:363 (6432): 1222-1226
被引量:246
标识
DOI:10.1126/science.aau5870
摘要
Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor-independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell's transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition.
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