Satellite Repeats Identify X Chromatin for Dosage Compensation in Drosophila melanogaster Males

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.