剂量补偿和MSL复合物研究进展

剂量补偿效应(Dosage compensation effect)广泛存在于两性真核生物,是基于性别决定、平衡不同性别间基因转录水平的遗传效应。MSL复合物(Male-specific lethal complex)是果蝇剂量补偿机制的核心,它乙酰化雄性果蝇X染色体上一些特定的位点,双倍激活X连锁活跃基因的转录,从而弥补雄性果蝇只具有单一条X染色体的不足。目前,已对果蝇MSL复合物各主要成分进行了结构分析,大体了解了各组分间的相互作用位点,并对该复合物的识别机制进行了大量的研究。与果蝇不同,哺乳动物是通过雌性个体一条X染色体的失活来实现剂量补偿。虽然哺乳动物MSL复合物的组成已被鉴定,但对其功能的研究还处于初步阶段。迄今为止,对硬骨鱼类剂量补偿及MSL复合物的研究极少。文章概括了线虫、果蝇和哺乳动物各物种剂量补偿机制的异同,综述了果蝇MSL复合物及其剂量补偿机制作用机理的研究进展,并提出有待解决的问题,同时利用同线性分析发现了不同鱼类msl3基因的多样性,为今后继续研究各物种的剂量补偿机制提供基础资料和研究方向。

Research advance of dosage compensation and MSL complex

Dosage compensation effect, which exists widely in eukaryotes with sexual reproduction, is an essential biological process that equalizes the level of gene expression between genders based on sex determination. In Drosophila, the male-specific lethal (MSL) complex mediates dosage compensation by acetylating histone H4 lysine K16 on nucleosome of some specific sites on the male X chromosome, globally upregulates twofold expression of active X-linked genes from the single X chromosome, and makes up for the shortage that the male has only one single X chromosome in male Drosophila. Up to date, the structure of basic components of MSL complex, which consists of at least five protein subunits and two non-coding RNAs, has already been revealed, and the interaction sites among these components have also been generally identified. Furthermore, abundant researches on recognition mechanism of the complex have been published. In contrast, many studies have revealed that mammalian dosage compensation functions by silencing gene expression from one of the two X chromosomes in females. The main components of mammalian MSL complex have already been identified, but the knowledge of their function is limited. Up to now, research of MSLs in teleosts is scarcely studied. This review summarizes the similarities and differences among dosage compensation mechanisms of nematodes, fruit flies and mammals, introduces the recent research advances in MSL complex, as well as molecular mechanism of dosage compensation in fruit fly, and finally addresses some problems to be resolved. Meanwhile, the diversity of msl3 gene in fishes is found by synteny analysis. This information might provide insightful directions for future research on the mechanisms of dosage compensation in various species.