Carmi I, Kopczynski J B, Meyer B J
Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.
Nature. 1998 Nov 12;396(6707):168-73. doi: 10.1038/24164.
Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.
许多门的生物通过区分一条X染色体和两条X染色体来确定性别命运。在这里，我们使用模式生物秀丽隐杆线虫，从分子细节上剖析这种X染色体计数机制。在这种线虫中，X染色体上的几个基因（称为X信号元件）通过控制性别决定基因xol-1的活性来传递X染色体剂量。xol-1在活跃时决定雄性（XO）命运，在不活跃时决定雌雄同体（XX）命运。到目前为止描述的唯一X信号元件在转录后抑制xol-1，但在XX动物中，xol-1通过转录和转录后机制被抑制。在这里，我们鉴定出一种核激素受体同源物SEX-1，它调节xol-1的转录。我们表明，sex-1对X染色体计数至关重要：改变XX或XO胚胎中的sex-1基因剂量会导致性别转变，并因剂量补偿不足（雌雄同体特有的使两性之间X基因表达相等的过程）而死亡。SEX-1蛋白直接作用于xol-1，在体内与其启动子结合，并在XX胚胎中抑制xol-1转录。因此，xol-1是初级性别决定信号的直接分子靶点，核激素受体的剂量有助于传递X染色体数量以确定线虫性别。
