Global regulation of the Drosophila melanogaster 4th chromosome

Wayne State University, Detroit MI

Investigators

Abstract

Drosophila melanogaster has highly differentiated sex chromosomes. A similar ratio of X-linked to autosomal gene products must be maintained in XX females and XY males. This is accomplished by an RNA and protein complex that coats the male X chromosome and modulates expression. The roX1 and roX2 (RNA on the X 1 and -2) transcripts ensure X-localization of the associated Male Specific Lethal (MSL) proteins. Elimination of both roX transcripts reduces X-linked gene expression in males. Surprisingly, expression of the entire 4th chromosome is also reduced. Elimination of MLE, one of the MSL proteins, also reduces expression of the male 4th chromosome but has no effect in females. MSL2, another member of the MSL complex, is not necessary for 4th chromosome expression in S2 cells. The notion that the 4th chromosome may be derived from an ancestral X chromosome makes these observations particularly exciting. This research will explore the hypothesis that elements of the X chromosome dosage compensation machinery also regulate the 4th chromosome of D. melanogaster, and constitute a second chromosome-wide epigenetic system in flies. This project will establish the genetic basis of 4th chromosome regulation. This research will enhance understanding of chromosome targeting and modification systems. It addresses a novel aspect of sex chromosome evolution: how X chromatin becomes autosomal. This project will involve training of graduate and undergraduate students at Wayne State University, which has an exceptionally diverse student population that includes underserved urban and immigrant populations.