Determining the mechanism of monoallelic expression in Drosophila melanogaster
02 / 2008 - 08 / 2010
Monoallelic expression, involving the complete silencing of one allele in a diploid cell, is an important mechanism of gene regulation in mammals. Mis-regulation of monoallelic expression is the basis for a wide array of diseases, including neurological disorders and cancers. The mechanism of monoallelic expression is still not fully understood and unraveling it is hampered by the complexity of mammalian systems. We observed for the first time true monoallelic expression in Drosophila melanogaster, where only the Y-chromosomal, but not the X-chromosomal rDNA loci are transcribed in male diploid cells. In contrast, both X-chromosomal rDNA loci are expressed in female cells. This allows us to study monoallelic expression in the genetic tractable Drosophila system. My goal is to define the mechanism of monoallelic expression in Drosophila melanogaster, utilizing rDNA expression as a readout. Furthermore, I will identify additional differentially expressed genes. In summary, I will 1) determine whether a Y-chromosomal sequence element, parental imprinting, or the sex of a fly is involved in regulating monoallelic expression; 2) map potential Y-chromosomal sequence elements; 3) determine the role of non-coding RNAs, chromosome pairing and epigenetic factors; and 4) identify additional differentially expressed genes by Solexa sequencing of a heterozygous Drosophila strain, exploiting single nucleotide polymorphisms. My findings will likely contribute to the understanding of human diseases resulting from mis-regulation of monoallelic expression, and will aid the identification of additional human genes that are differentially expressed.