Path to equality strewn with roX.

Male flies hypertranscribe most genes along their single X chromosome to match the output of females with two X chromosomes. This is mediated by chromatin modifications carried out by the MSL complex composed of noncoding roX RNA and at least five MSL proteins. New results indicate that one of these subunits, the MOF acetyltransferase, not only acts on histone H4, but on itself and MSL3. Cycles of covalent modifications of the MSL subunits may determine the proper level of hypertranscription or control cis spreading along the chromosome. The MSL complex binds to the roX genes, the very source of the RNA component of the complex. New details of how this interaction occurs hint at a possible autoregulatory function. Finally, despite intensive efforts, the molecular mechanism by which the MSL complex distinguishes the X from the autosomes remains a mystery. The MSL complex is able to spread epigenetically from the site of roX transcription, and recent work has defined the conditions that control local cis spreading. However, it is equally clear that soluble MSL complex can distinguish the X chromosome from autosomes. Reconciling all these findings into a unified model presents a challenge.