Bai Xiaoying, Alekseyenko Artyom A, Kuroda Mitzi I
Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
EMBO J. 2004 Jul 21;23(14):2853-61. doi: 10.1038/sj.emboj.7600299. Epub 2004 Jul 1.
In Drosophila, dosage compensation is controlled by the male-specific lethal (MSL) complex consisting of at least five proteins and two noncoding RNAs, roX1 and roX2. The roX RNAs function in targeting MSL complex to the X chromosome, and roX transgenes can nucleate spreading of the MSL complex into flanking chromatin when inserted on an autosome. An MSL-binding site (DHS, DNaseI hypersensitive site) has been identified in each roX gene. Here, we investigate the functions of the DHS using transgenic deletion analyses and reporter assays. We find that MSL interaction with the DHS counteracts constitutive repression at roX1, resulting in male-specific expression of roX1 RNA. Surprisingly, the DHS is not required for initiation of cis spreading of MSL complex, instead local transcription of roX RNAs correlates with extensive spreading.
在果蝇中,剂量补偿由雄性特异性致死(MSL)复合物控制,该复合物至少由五种蛋白质以及两种非编码RNA(roX1和roX2)组成。roX RNA的功能是将MSL复合物靶向到X染色体上,并且当roX转基因插入常染色体时,它可以促使MSL复合物扩散到侧翼染色质中。在每个roX基因中都已鉴定出一个MSL结合位点(DHS,DNaseI超敏位点)。在这里,我们使用转基因缺失分析和报告基因检测来研究DHS的功能。我们发现MSL与DHS的相互作用抵消了roX1处的组成型抑制作用,从而导致roX1 RNA的雄性特异性表达。令人惊讶的是,DHS对于MSL复合物的顺式扩散起始并非必需,相反,roX RNA的局部转录与广泛扩散相关。