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The effects of IIS/TOR signaling on gene expression in Drosophila males and females: IIS/TOR impacts sex-differential gene expression

ABSTRACT: The insulin signaling pathway is known to interact directly and indirectly with the sex determination regulatory hierarchy, playing a role in directing sexually dimorphic traits. To understand the degree to which the insulin signaling pathway contributes to sexually dimorphic gene expression in adult animals, we examined the effect of perturbation of the pathway on gene expression in male and female Drosophila. Our data reveal a large effect of insulin signaling on expression in adult males and females, with greater than 50% of genes examined changing expression. Males and females have a shared gene expression response to knock-down of InR function, with significant enrichment for pathways involved in metabolism. However, perturbation of insulin signaling has a greater impact on gene expression in males, with more genes changing expression and with a larger magnitude of changes overall. Primarily as a consequence of the response in males, we find that reduced insulin signaling results in a striking increase in sex-differential expression. This includes sex-differences in expression of immune, defense and stress response genes, as well as genes in the insulin signaling pathway itself. Our results demonstrate that perturbation of insulin signaling results in thousands of genes displaying sex differences in expression that are not differentially expressed in control conditions. Thus, insulin signaling may play a role in variability of sex-differential expression observed in studies of adult somatic tissues.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE112836 | GEO | 2018/10/06

REPOSITORIES: GEO

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Project description:There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnlγ). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes. Small intestine and colon were isolated from two-week old pups of dams fed a low-fat diet and subjected to gene expression profiling

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The effects of IIS/TOR signaling on gene expression in Drosophila males and females: IIS/TOR impacts sex-differential gene expression

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