Harley Vincent R, Clarkson Michael J, Argentaro Anthony
Prince Henry's Institute of Medical Research, Clayton 3168, Victoria, Australia.
Endocr Rev. 2003 Aug;24(4):466-87. doi: 10.1210/er.2002-0025.
Despite 12 yr since the discovery of SRY, little is known at the molecular level about how SRY and the SRY-related protein, SOX9 [SRY-related high-mobility group (HMG) box 9], initiate the program of gene expression required to commit the bipotential embryonic gonad to develop into a testis rather than an ovary. Analysis of SRY and SOX9 clinical mutant proteins and XX mice transgenic for testis-determining genes have provided some insight into their normal functions. SRY and SOX9 contain an HMG domain, a DNA-binding motif. The HMG domain plays a central role, being highly conserved between species and the site of nearly all missense mutations causing XY gonadal dysgenesis. SRY and SOX9 are architectural transcription factors; their HMG domain is capable of directing nuclear import and DNA bending. Whether SRY and SOX9 activate testis-forming genes, repress ovary-forming genes, or both remains speculative until downstream DNA target genes are identified. However, factors that control SRY and SOX9 gene expression have been identified, as have a dozen sex-determining genes, allowing some of the pieces in this molecular genetic puzzle to be connected. Many genes, however, remain unidentified, because in the majority of cases of XY females and in all cases of XX males lacking SRY, the mutated gene is unknown.
尽管自发现SRY已有12年，但在分子水平上，关于SRY以及与SRY相关的蛋白SOX9[SRY相关的高迁移率族（HMG）盒9]如何启动双潜能胚胎性腺发育为睾丸而非卵巢所需的基因表达程序，人们所知甚少。对SRY和SOX9临床突变蛋白以及携带睾丸决定基因的XX转基因小鼠的分析，为了解它们的正常功能提供了一些线索。SRY和SOX9含有一个HMG结构域，这是一种DNA结合基序。HMG结构域起着核心作用，在物种间高度保守，并且是几乎所有导致XY性发育不全的错义突变位点。SRY和SOX9是结构转录因子；它们的HMG结构域能够指导核转运和DNA弯曲。在确定下游DNA靶基因之前，SRY和SOX9是激活睾丸形成基因、抑制卵巢形成基因，还是两者兼而有之，仍属推测。然而，已经确定了控制SRY和SOX9基因表达的因子，也确定了十几个性别决定基因，使得这个分子遗传学谜题中的一些片段能够联系起来。然而，许多基因仍未被识别，因为在大多数XY女性病例以及所有缺乏SRY的XX男性病例中，突变基因尚不清楚。
