Chromodomains are protein-RNA interaction modules

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(1). Dosage compensation is an epigenetic process involving the specific acetylation of histone H4 at lysine 16 by the histone acetyltransferase MOF2-5. Although MOF is expressed in both sexes, it only associates with the X chromosome in males. Its absence causes male-specific lethality(6). MOF is part of a chromosome-associated complex comprising male-specific lethal (MSL) proteins and at least one non-coding roX RNA(7). 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.