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Case essay: bioinformatics
Computational inference of cis-regulatory elements involved in transcriptional regulation of sex-biased gene expression in Drosophila
Supervisors: Dr. Max Reuter | Dr. Vincent Plagnol
Download: PDF (~1.5 MB)
Drosophila sex-determination mechanism is a prime example of complex multi-level regulatory network involving transcriptional regulation and alternative splicing of pre-messenger RNA. The different pathways involved have been extensively described, including the role of key molecules such as doublesex or fruitless, which are thought to regulate the expression of particular genes responsible for sex-specific phenotypes. However, it is yet to be determined if they directly interact with the DNA or if an intermediate layer of regulators comes into play.
Proportions of sex-biased genes (A) and Relative frequency distribution of the motif distance from the transcription initiation site (B)
The goal of this case essay was to determine if a cis-regulatory element present in the 5’ flanking region of certain Drosophila malanogaster genes could be responsible for their sex-biased expression. Different approaches to computational inference of DNA motifs were integrated in a workflow designed to facilitate the analysis of large amounts of sequences with, as a starting point, sex-biased expression data that was extracted from the literature. A custom R framework was also developed to allow seamless integration of the various tools and to facilitate data visualization.
Motifs with an ‘ATCGAT’ core were found to be significantly overrepresented upstream of female-biased genes and the proportion of male-biased genes with at least one instance of the sequence in their 5’ flanking region was bellow what was observed for a random control distribution. Similar results were obtained for six related Drosophila species. The motif was identified as a binding sequence for BEAF-32 (32 kDa boundary element-association factor) but more interestingly, it also corresponds to the previously reported DNA replicated-related element (DRE), which is the central element of a vast regulatory network. Results seem to indicate that the CRE/DREF system might also have a sex-specific regulatory function, mostly independent of previously described mechanisms.
