Non-canonical Drosophila X chromosome dosage compensation and repressive topologically-associated domains

Abstract

BackgroundIn animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in male Drosophila, there is a dosage compensation complex (MSL), that equilibrates X-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 the X, which has no pairing partner, then de-repression could contribute to male dosage compensation.\n\nResultsWe asked whether different chromatin states or topological associations correlate with X chromosome dosage compensation, especially in regions with little MSL occupancy. Our analyses demonstrated that male X chromosome 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.\n\nConclusionsOur 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 of C. elegans, where enhanced recruitment of X chromosomes to the nuclear lamina dampens X chromosome expression as part of the dosage compensation response in XX individuals.