Abstract
A common feature of sex chromosomes is coordinated regulation of X-linked genes in one sex. Drosophila melanogaster males have one X chromosome, whereas females have two. The resulting imbalance in gene dosage is corrected by increased expression from the single X chromosome of males, a process known as dosage compensation. In flies, compensation involves recruitment of the male-specific lethal (MSL) complex to X-linked genes and modification of chromatin to increase expression. The extraordinary selectivity of the MSL complex for the X chromosome has never been explained. We previously demonstrated that the small interfering RNA (siRNA) pathway and siRNA from a family of X-linked satellite repeats (1.688(X) repeats) promote X recognition. Now, we test the ability of 1.688(X) DNA to attract compensation to genes nearby and report that autosomal integration of 1.688(X) repeats increases MSL recruitment and gene expression in surrounding regions. Placement of 1.688(X) repeats opposite a lethal autosomal deletion achieves partial rescue of males, demonstrating functional compensation of autosomal chromatin. Females block formation of the MSL complex and are not rescued. The 1.688(X) repeats are therefore cis-acting elements that guide dosage compensation. Furthermore, 1.688(X) siRNA enhances rescue of males with a lethal deletion but only when repeat DNA is present on the intact homolog. We propose that the siRNA pathway promotes X recognition by enhancing the ability of 1.688(X) DNA to attract compensation in cis. The dense and near-exclusive distribution of 1.688(X) sequences along the X chromosome suggests that they play a primary role in determining X identity during dosage compensation.