The activation potential of MOF is constrained for dosage compensation, MBD-R2 transcriptome analysis

The H4K16 acetyltransferase MOF plays a crucial role in dosage compensation in Drosophila, but has additional, global functions in gene control. We compared the molecular context and effect of MOF activity in male and female flies combining chromosome-wide mapping and transcriptome studies with analyses of defined reporter loci in transgenic flies. MOF distributes dynamically between two types of complexes, the Dosage Compensation Complex (DCC) and complexes containing MBD-R2, a global facilitator of transcription. These different targeting principles define the distribution of MOF between the X chromosome and autosomes and at transcription units with 5’ or 3’ enrichment. The male X chromosome differs from all other chromosomes in that H4K16 acetylation levels do not correlate with transcription output. The reconstitution of this phenomenon at a model locus revealed that the activation potential of MOF is constrained in male cells in the context of the DCC to arrive at the two-fold activation of transcription characteristic of dosage compensation. Drosophila SL2 cells were treated with RNAi against two different constructs targeting the MBD-R2 transcript (M1 and M2, "rep" represents "biological replicate", GST RNAi and one no dsRNA sample ("control").