Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance.
Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance.
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DOI：
10.1093/nar/gkq491
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发表时间：
2010-10
影响因子：
14.9
通讯作者：
Seo SB
中科院分区：
文献类型：
--
作者：
Kim SM;Kim JY;Choe NW;Cho IH;Kim JR;Kim DW;Seol JE;Lee SE;Kook H;Nam KI;Kook H;Bhak YY;Seo SB
组蛋白甲基转移酶和去甲基化酶对组蛋白赖氨酸甲基化状态的动态交换在染色质结构和转录调控中被认为是一个重要的因素。利用免疫亲和TAP分析，我们纯化了WHISTLE相互作用蛋白复合物，其中包括热休克蛋白HSP 90 α和含有组蛋白去甲基化酶JMJD 1C的jumonji C结构域。在这项研究中，我们证明了JMJD 1C特异性地去甲基化组蛋白H3 K9单甲基化和二甲基化，并介导转录激活。我们还提供了证据表明，WHISTLE和JMJD 1C通过SF-1介导的转录调节类固醇生成标记物p450 c17的表达，在小鼠睾丸发育中发挥作用。此外，我们证明了WHISTLE通过SF-1被招募到p450 c17启动子，并抑制类固醇生成的青春期前阶段的转录，之后JMJD 1C取代WHISTLE并通过SF-1介导的相互作用激活靶基因的表达。我们的研究结果表明，由HMTase WHISTLE和去甲基化酶JMJD 1C介导的组蛋白甲基化平衡在小鼠睾丸发育中发挥转录调节功能。
The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90α and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation. We also provide evidence suggesting that both WHISTLE and JMJD1C performs functions in the development of mouse testes by regulating the expression of the steroidogenesis marker, p450c17, via SF-1-mediated transcription. Furthermore, we demonstrate that WHISTLE is recruited to the p450c17 promoter via SF-1 and represses the transcription of prepubertal stages of steroidogenesis, after which JMJD1C replaces WHISTLE and activates the expression of target genes via SF-1-mediated interactions. Our results demonstrate that the histone methylation balance mediated by HMTase WHISTLE and demethylase JMJD1C perform a transcriptional regulatory function in mouse testis development.
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影响因子：
4
作者：
Knebel, Julia;De Haro, Luciano;Janknecht, Ralf
通讯作者：
Janknecht, Ralf
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
DOI：
10.1016/j.bbrc.2006.04.095
发表时间：
2006-06-23
影响因子：
3.1
作者：
Kim, Sung Mi;Kee, Hae Jin;Seo, Sang Beom
通讯作者：
Seo, Sang Beom
影响因子：
56.9
作者：
Lee, Min Gyu;Villa, Raffaella;Shiekhattar, Ramin
通讯作者：
Shiekhattar, Ramin
影响因子：
4.8
作者：
Shirato, Haruki;Ogawa, Satoko;Takeuchi, Takashi
通讯作者：
Takeuchi, Takashi