Hargitai Balázs, Kutnyánszky Vera, Blauwkamp Timothy A, Steták Attila, Csankovszki Györgyi, Takács-Vellai Krisztina, Vellai Tibor
Department of Genetics, Eötvös Loránd University, Budapest H-1117, Hungary.
Development. 2009 Dec;136(23):3881-7. doi: 10.1242/dev.034637.
In the nematode Caenorhabditis elegans, sex is determined by the ratio of X chromosomes to sets of autosomes: XX animals (2X:2A=1.0) develop as hermaphrodites and XO animals (1X:2A=0.5) develop as males. TRA-1, the worm ortholog of Drosophila Cubitus interruptus and mammalian Gli (Glioma-associated homolog) proteins, is the terminal transcription factor of the C. elegans sex-determination pathway, which specifies hermaphrodite fate by repressing male-specific genes. Here we identify a consensus TRA-1 binding site in the regulatory region of xol-1, the master switch gene controlling sex determination and dosage compensation. xol-1 is normally expressed in males, where it promotes male development and prevents dosage compensation. We show that TRA-1 binds to the consensus site in the xol-1 promoter in vitro and inhibits the expression of xol-1 in XX animals in vivo. Furthermore, inactivation of tra-1 enhances, whereas hyperactivation of tra-1 suppresses, lethality in animals with elevated xol-1 activity. These data imply the existence of a regulatory feedback loop within the C. elegans sex-determination and dosage-compensation cascade that ensures the accurate dose of X-linked genes in cells destined to adopt hermaphrodite fate.
在秀丽隐杆线虫中，性别由X染色体与常染色体组的比例决定：XX动物（2X:2A = 1.0）发育为雌雄同体，XO动物（1X:2A = 0.5）发育为雄性。TRA-1是果蝇间断翅脉蛋白和哺乳动物Gli（胶质瘤相关同源物）蛋白在蠕虫中的直系同源物，是秀丽隐杆线虫性别决定途径的终端转录因子，它通过抑制雄性特异性基因来确定雌雄同体的命运。在这里，我们在xol-1的调控区域中鉴定出一个共有TRA-1结合位点，xol-1是控制性别决定和剂量补偿的主开关基因。xol-1通常在雄性中表达，在那里它促进雄性发育并阻止剂量补偿。我们表明，TRA-1在体外与xol-1启动子中的共有位点结合，并在体内抑制XX动物中xol-1的表达。此外，tra-1的失活增强了xol-1活性升高的动物的致死率，而tra-1的过度激活则抑制了这种致死率。这些数据表明，在秀丽隐杆线虫性别决定和剂量补偿级联反应中存在一个调控反馈环，以确保注定发育为雌雄同体的细胞中X连锁基因的准确剂量。
