Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Curr Top Dev Biol. 2019;134:195-221. doi: 10.1016/bs.ctdb.2019.01.008. Epub 2019 Feb 18.
Mammalian sex determination is triggered by activation of the mammalian sex-determining gene, Sry, in a spatially and temporally controlled manner. Because reduced or delayed Sry expression results in male-to-female sex reversal, male development is highly dependent on the accurate transcription of Sry. SRY dysregulation is a potential cause of human disorders of sex development (DSD). In addition to changes in DNA sequences, gene expression is regulated by epigenetic mechanisms. Epigenetic regulation ensures spatial and temporal accuracy of the expression of developmentally regulated genes. Epigenetic regulation such as histone tail modification, DNA methylation, chromatin remodeling, and non-coding RNA regulation engages several biological processes in multicellular organisms. In recent years, it has been revealed that various types of epigenetic regulation are involved in accurate gonadal differentiation in mammals. In particular, histone modification plays an integral part in sex determination, which is the first step of gonadal differentiation. Here, we focus on the findings on the epigenetic modifications that regulate Sry expression. Finally, we discuss the role of metabolism that potentially alters the epigenetic state in response to environmental cues.
哺乳动物的性别决定是通过 Sry 基因在空间和时间上的激活触发的。由于 Sry 表达的减少或延迟会导致雄性到雌性的性别逆转，因此雄性发育高度依赖于 Sry 的准确转录。SRY 失调是人类性别发育障碍 (DSD) 的潜在原因。除了 DNA 序列的变化外，基因表达还受到表观遗传机制的调控。表观遗传调控确保了发育调节基因表达的时空准确性。表观遗传调控，如组蛋白尾部修饰、DNA 甲基化、染色质重塑和非编码 RNA 调控，涉及多细胞生物中的几个生物学过程。近年来，人们发现各种类型的表观遗传调控参与了哺乳动物中精确的性腺分化。特别是，组蛋白修饰在性别决定中起着不可或缺的作用，性别决定是性腺分化的第一步。在这里，我们重点介绍了调节 Sry 表达的表观遗传修饰的研究结果。最后，我们讨论了代谢在潜在改变表观遗传状态以响应环境线索方面的作用。
