Non-canonicalDrosophilaX chromosome dosage compensation and repressive topologically-associated domains

AbstractBackgroundIn animals withXYsex chromosomes,X-linked genes from a singleXchromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in maleDrosophila, there is a dosage compensation complex (MSL), that equilibratesX-linked gene expression with the autosomes. There are other potential contributions to dosage compensation. Hemizygous autosomal genes located in repressive chromatin domains are often de-repressed. If this homolog-dependent repression occurs on theX, which has no pairing partner, then de-repression could contribute to male dosage compensation.ResultsWe asked whether different chromatin states or topological associations correlate withXchromosome dosage compensation, especially in regions with little MSL occupancy. Our analyses demonstrated that maleXchromosome genes that are located in repressive chromatin states are depleted of MSL occupancy, however they show dosage compensation. The genes in these repressive regions were also less sensitive to knockdown of MSL components.ConclusionsOur results suggest that this non-canonical dosage compensation is due to the same trans-acting de-repression that occurs on autosomes. This mechanism would facilitate immediate compensation during the evolution of sex chromosomes from autosomes. This mechanism is similar to that ofC. elegans, where enhanced recruitment ofXchromosomes to the nuclear lamina dampensXchromosome expression as part of the dosage compensation response inXXindividuals.