Open Access Dissertation
Date of Award
Victoria H. Meller
roX1 is a long non-coding RNA involved in the chromosome-wide gene regulation that occurs during dosage compensation in Drosophila. Dosage compensation in Drosophila melanogaster occurs by a global two-fold increase of transcription from the single male X chromosome. This essential process compensates for X chromosome monosomy. The male-specific lethal (MSL) complex, containing five proteins, localizes to the male X chromosome and alters chromatin to modify gene expression. roX1 and roX2 RNAs are redundant components of MSL complex that are required for its exclusive X-localization. Recent studies in our lab have revealed a second role of roX RNAs in heterochromatic gene expression in males. The roX-dependent heterochromatic regulation system involves some, but not all, MSL proteins. Although all components of this system discovered now are expressed in females, microarray analysis showed that the roX1 RNA has no detectable affect on expression of both X-linked and heterochromatic genes in females. Therefore, like dosage compensation, the roX-dependent heterochromatic regulation system is also limited to males. The differential regulation of heterochromatic genes in males and females may reflect the differences of heterochromatin between them. Previous studies of roX1 mutants and transgenes have identified a large region at the 5' end of roX1 that is necessary for X-localization of the MSL complex. To dissect the function of this region, roX1 transgenes containing portions of the 5' end were generated and analyzed. Multiple redundant elements contributing to X chromosome targeting were found to be present throughout the 5' end of roX1. These roX1 transgenes display different stability, but all can partially restore X-linked gene expression in a roX1 roX2 mutant. One portion of this region is uniquely able to promote MSL complex spreading from sites of transcription. Previous model of MSL spreading suggested a verse relevance of roX1 transcript abundance and the ability to spread. However, the ability of this region to direct MSL spreading is not relevant to its abundance. The activities I have detected are hypothesized to be regulated by choice of transcription start site, alternative splicing and/or transcript stability.
Kong, Ying, "Rox1 function in dosage compensation: structural / functional analysis of a non-coding rna" (2012). Wayne State University Dissertations. Paper 415.