Mutations in the Transcription Elongation Factor SPT5 Disrupt a Reporter for Dosage Compensation in Drosophila

In Drosophila, the MSL (Male Specific Lethal) complex up regulates transcription of active genes on the single male X-chromosome to equalize gene expression between sexes. One model argues that the MSL complex acts upon the elongation step of transcription rather than initiation. In an unbiased forward genetic screen for new factors required for dosage compensation, we found that mutations in the universally conserved transcription elongation factor Spt5 lower MSL complex dependent expression from the miniwhite reporter gene in vivo. We show that SPT5 interacts directly with MSL1 in vitro and is required downstream of MSL complex recruitment, providing the first mechanistic data corroborating the elongation model of dosage compensation.在果蝇（Drosophila）中，雄性特异性致死复合物（Male Specific Lethal，MSL）可上调单一雄性X染色体上活跃基因的转录水平，以实现两性间基因表达的均衡。有假说提出，MSL复合物并非作用于转录起始阶段，而是靶向转录延伸步骤。在一项针对剂量补偿所需全新因子的无偏正向遗传筛选中，我们发现泛保守转录延伸因子Spt5（transcription elongation factor Spt5）的突变，可在体内降低依赖MSL复合物的miniwhite报告基因（miniwhite reporter gene）的表达量。我们证实，SPT5可在体外与MSL1直接相互作用，且在MSL复合物招募的下游环节发挥功能，这为剂量补偿的延伸作用模型提供了首个机制层面的实验佐证。