Stable chromosomal association of MSL2 defines a dosage-compensated nuclear compartment.

Dosage compensation in Drosophila is controlled by a complex (DCC) of proteins and noncoding RNA that binds specifically to the male X chromosome and leads to fine-tuning of transcription. Here, we employ male SL2 cells to characterize DCC function and dynamics during steady state of dosage compensation. Knocking down the key regulator of dosage compensation, male-specific-lethal 2 (MSL2), leads to loss of propagation of histone H4 lysine 16 acetylation and of the twofold elevation of transcription characteristic of the compensated male X chromosome.

Functional integration of the histone acetyltransferase MOF into the dosage compensation complex.

Dosage compensation in flies involves doubling the transcription of genes on the single male X chromosome to match the combined expression level of the two female X chromosomes. Crucial for this activation is the acetylation of histone H4 by the histone acetyltransferase (HAT) MOF. In male cells, MOF resides in a complex (dosage compensation complex, DCC) with MSL proteins and noncoding roX RNA.