Drosophila melanogaster employs nuclear architecture for recruitment of dosage compensation

Drosophila melanogaster males increase expression from their single X chromosome to match the expression from two female X chromosomes. Increased expression involves recruitment of the Male Specific Lethal (MSL) complex to X-linked genes and modification of chromatin by this complex. How X-linked genes are selectively identified remains unclear, but cis-acting recruiting elements are involved. Chromatin Entry Sites (CES) bind an adapter protein that directly recruits the MSL complex. In addition, a class of AT-rich satellites, the 1.688X repeats, are enriched on the X and facilitate compensation of nearby genes. How these elements cooperate to identify the X is unknown. Nuclear architecture influences dosage compensation in many organisms. In this study we test the idea that factors involved in nuclear architecture participate in recruitment by the CES and 1.688X repeats. We find genetic interactions between mutations that reduce X recognition and factors that govern chromatin structure, silencing, remodeling and insulation, suggesting roles in X recognition. A reporter for recruitment revealed that Heterochromatin Protein 2 (HP2) and Scaffold Attachment Factor-A (SAF-A) disrupt compensation but do not selectively influence recruitment by either element. In contrast, Imitation switch (ISWI), D1 and Nucleoporin 153kD (Nup153) contribute to recruitment by the CES and Centrosomal protein 190kD (Cp190) exerts a striking influence on recruitment by 1.688X repeats. These findings reveal that recruitment by the CES and 1.688X repeats involves nuclear organization. We propose that the use of cis-acting elements that engage complementary aspects of nuclear organization ensures robust X recognition.