Clough Emily, Jimenez Erin, Kim Yoo-Ah, Whitworth Cale, Neville Megan C, Hempel Leonie U, Pavlou Hania J, Chen Zhen-Xia, Sturgill David, Dale Ryan K, Smith Harold E, Przytycka Teresa M, Goodwin Stephen F, Van Doren Mark, Oliver Brian
National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Dev Cell. 2014 Dec 22;31(6):761-73. doi: 10.1016/j.devcel.2014.11.021.
Primary sex-determination "switches" evolve rapidly, but Doublesex (DSX)-related transcription factors (DMRTs) act downstream of these switches to control sexual development in most animal species. Drosophila dsx encodes female- and male-specific isoforms (DSX(F) and DSX(M)), but little is known about how dsx controls sexual development, whether DSX(F) and DSX(M) bind different targets, or how DSX proteins direct different outcomes in diverse tissues. We undertook genome-wide analyses to identify DSX targets using in vivo occupancy, binding site prediction, and evolutionary conservation. We find that DSX(F) and DSX(M) bind thousands of the same targets in multiple tissues in both sexes, yet these targets have sex- and tissue-specific functions. Interestingly, DSX targets show considerable overlap with targets identified for mouse DMRT1. DSX targets include transcription factors and signaling pathway components providing for direct and indirect regulation of sex-biased expression.
初级性别决定“开关”进化迅速,但与双性(DSX)相关的转录因子(DMRTs)在这些开关的下游起作用,以控制大多数动物物种的性别发育。果蝇dsx编码雌性和雄性特异性异构体(DSX(F)和DSX(M)),但对于dsx如何控制性别发育、DSX(F)和DSX(M)是否结合不同的靶标,或者DSX蛋白如何在不同组织中引导不同的结果,我们知之甚少。我们进行了全基因组分析,以利用体内占据、结合位点预测和进化保守性来鉴定DSX靶标。我们发现,DSX(F)和DSX(M)在两性的多种组织中结合数千个相同的靶标,但这些靶标具有性别和组织特异性功能。有趣的是,DSX靶标与为小鼠DMRT1鉴定的靶标有相当大的重叠。DSX靶标包括转录因子和信号通路成分,可直接和间接调节性别偏向表达。