Akhtar A, Zink D, Becker P B
Adolf Butenandt-Institut, Molekularbiologie, Ludwig-Maximilians-Universität, München, Germany.
Nature. 2000 Sep 21;407(6802):405-9. doi: 10.1038/35030169.
In Drosophila, compensation for the reduced dosage of genes located on the single male X chromosome involves doubling their expression in relation to their counterparts on female X chromosomes. Dosage compensation is an epigenetic process involving the specific acetylation of histone H4 at lysine 16 by the histone acetyltransferase MOF. Although MOF is expressed in both sexes, it only associates with the X chromosome in males. Its absence causes male-specific lethality. MOF is part of a chromosome-associated complex comprising male-specific lethal (MSL) proteins and at least one non-coding roX RNA. How MOF is integrated into the dosage compensation complex is unknown. Here we show that association of MOF with the male X chromosome depends on its interaction with RNA. MOF specifically binds through its chromodomain to roX2 RNA in vivo. In vitro analyses of the MOF and MSL-3 chromodomains indicate that these chromodomains may function as RNA interaction modules. Their interaction with non-coding RNA may target regulators to specific chromosomal sites.
在果蝇中，对位于单个雄性X染色体上的基因剂量减少的补偿涉及使其表达相对于雌性X染色体上的对应基因加倍。剂量补偿是一个表观遗传过程，涉及组蛋白乙酰转移酶MOF对组蛋白H4赖氨酸16位点的特异性乙酰化。尽管MOF在两性中均有表达，但它仅在雄性中与X染色体结合。其缺失会导致雄性特异性致死。MOF是一个与染色体相关的复合物的一部分，该复合物包含雄性特异性致死（MSL）蛋白和至少一种非编码roX RNA。MOF如何整合到剂量补偿复合物中尚不清楚。在这里，我们表明MOF与雄性X染色体的结合取决于它与RNA的相互作用。MOF在体内通过其色域特异性结合roX2 RNA。对MOF和MSL-3色域的体外分析表明，这些色域可能作为RNA相互作用模块发挥作用。它们与非编码RNA的相互作用可能将调节因子靶向特定的染色体位点。
