The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF
The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF
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DOI：
10.1074/jbc.m804578200
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发表时间：
2008-12-26
影响因子：
4.8
通讯作者：
Staller, Peter
中科院分区：
文献类型：
--
作者：
Beyer, Sophie;Kristensen, Malene Maag;Staller, Peter
翻译后组蛋白修饰用于存储表观遗传信息和控制核小体组装和非组蛋白的募集。组蛋白甲基化发生在精氨酸和赖氨酸残基上，并参与基因转录的调控。这些修饰的动态控制是由组蛋白甲基转移酶和最近发现的组蛋白去甲基化酶施加的。本研究表明，缺氧诱导因子HIF-1 α结合到珠猴家族组蛋白去甲基化酶JMJD1A和JMJD2B编码基因的特定识别位点并诱导其表达。因此，缺氧细胞表达JMJD1A和JMJD2B mRNA和蛋白水平升高。此外，我们发现在失去von Hippel Lindau肿瘤抑制蛋白VHL的肾癌细胞中，JMJD1A和JMJD2B的表达增加，从而显示缺氧诱导因子的表达失调。对异位表达的JMJD1A和JMJD2B的研究表明，这两种蛋白在缺氧条件下保持其组蛋白赖氨酸去甲基化酶活性，从而可能影响缺氧基因的表达程序。
Posttranslational histone modifications serve to store epigenetic information and control both nucleosome assembly and recruitment of non-histone proteins. Histone methylation occurs on arginine and lysine residues and is involved in the regulation of gene transcription. A dynamic control of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases. Here we show that the hypoxia-inducible factor HIF-1 alpha binds to specific recognition sites in the genes encoding the jumonji family histone demethylases JMJD1A and JMJD2B and induces their expression. Accordingly, hypoxic cells express elevated levels of JMJD1A and JMJD2B mRNA and protein. Furthermore, we find increased expression of JMJD1A and JMJD2B in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of hypoxia-inducible factor. Studies on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program.