Epigenetic Regulation of Mouse Sex Determination by the Histone Demethylase Jmjd1a
Epigenetic Regulation of Mouse Sex Determination by the Histone Demethylase Jmjd1a
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DOI：
10.1126/science.1239864
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发表时间：
2013-09-06
期刊：
影响因子：
56.9
通讯作者：
Tachibana, Makoto
中科院分区：
文献类型：
--
作者：
Kuroki, Shunsuke;Matoba, Shogo;Tachibana, Makoto
发育基因表达是通过转录因子的功能和表观遗传状态（包括组蛋白修饰）之间的相互作用来定义的。虽然一些转录因子在哺乳动物性别决定中起着至关重要的作用，但表观遗传调控如何促进这一过程仍不清楚。我们在缺乏H3K9去甲基化酶Jmjd1a的小鼠中观察到雄性到雌性的性逆转，并发现Jmjd1a调节哺乳动物Y染色体性别决定基因Sry的表达。Jmjd1a通过调节H3K9me2标记直接正向调控Sry的表达。这些研究揭示了组蛋白去甲基化在哺乳动物性别决定中的关键作用。
Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status, including histone modification. Although several transcription factors play crucial roles in mammalian sex determination, how epigenetic regulation contributes to this process remains unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a and found that Jmjd1a regulates expression of the mammalian Y chromosome sex-determining gene Sry. Jmjd1a directly and positively controls Sry expression by regulating H3K9me2 marks. These studies reveal a pivotal role of histone demethylation in mammalian sex determination.