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Analysis of sexually dimorphic accumulation of taxoids identifies a female-specific MYB-bHLH complex involved in the paclitaxel biosynthesis of Taxus media

ABSTRACT: Taxol is an efficient anticancer drug accumulated in Taxus trees. Taxus media, a large-scale cultured species, is a dioecious woody tree with high taxol yielding. However, the sexually dimorphic accumulation of taxoids in T. media is largely unknown. Our study identified a large number of differentially accumulated metabolites and differentially expressed genes, revealing the comprehensive differences between the female and male T. media trees. LC-MS analysis confirmed the high accumulation of taxoids in the female trees. Expression analysis showed that most Taxol biosynthesis-related genes were predominantly expressed in the female trees. To investigate the regulation mechanism underlying the sexually dimorphic accumulation of taxoids, a female-specific expressed gene, TmMYB39, was identified and its full-length sequence was cloned. Multiple sequence alignment and phylogenetic analyses showed that TmMYB39 is a typical R2R3-MYB factor and the subcellular localization of TmMYB39 is shown to be the nucleus. Furthermore, Y2H and BiFC assays showed that TmMYB39 interacts with TmbHLH13. Partial promoter sequences of 10 taxol biosynthesis-related genes were isolated, which were used for screening of the MYB recognition elements. TmMYB39 binds to the promoters of several taxol-related genes, such as GGPPS, T7OH, T10OH, T13OH, and TBT genes. Interaction between TmMYB39 and TmbHLH13 affected the expression of GGPS and T10OH genes, suggesting that TmMYB39 might function in the regulation of taxol biosynthesis through a ‘MYB-bHLH’ module. Our data provided a potential explanation for the sexually dimorphic accumulation of taxoids.

ORGANISM(S): Taxus x media

PROVIDER: GSE175645 | GEO | 2021/05/28

REPOSITORIES: GEO

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Project description:Worldwide, fetal growth restriction (FGR) affects 7 to 10% of pregnancies, or roughly 20.5 million infants, each year. FGR not only increases neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR "programs" an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus, we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from male and female near-term FGR and normal-weight fetal lambs (N=4 in each group, 16 total), examined the preadipocytes' differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have lower cellular density compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.

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Project description:Sexually dimorphic traits are by definition exaggerated in one sex, which may arise from a history of sex-specific selection â in males, females, or both. If this exaggeration comes at a cost, exaggeration is expected to be greater in higher condition individuals (condition-dependent). Although studies using small numbers of morphological traits are generally supportive, this prediction has not been examined at a larger scale. We test this prediction across the trancriptome by determining the condition-dependence of sex-biased (dimorphic) gene expression. We find that high-condition populations are more sexually dimorphic in transcription than low-condition populations. High condition populations have more male-biased genes and more female-biased genes, and a greater degree of sexually dimorphic expression in these genes. Also, condition-dependence in male-biased genes was greater than in a set of unbiased genes. Interestingly, male-biased genes expressed in the testes were not more condition-dependent than those in the soma. By contrast, increased female-biased expression under high condition may be have occurred because of the greater contribution of the ovary-specific transcripts to the entire mRNA pool. We did not find any genomic signatures distinguishing the condition-dependent sex-biased genes. The degree of condition-dependent sexual dimorphism (CDSD) did not differ between the autosomes and the X-chromosome. There was only weak evidence that rates of evolution correlated with CDSD. We suggest that the sensitivity of both female-biased genes and male-biased genes to condition may be akin to the overall heightened sensitivity to condition that life-history and sexually selected traits tend to exhibit. Our results demonstrate that through condition-dependence, early life experience has dramatic effects on sexual dimorphism in the adult transcriptome. There were 8 biologically distinct samples. Each was replicated 6 times for a total of 48 biological samples on 24 arrays. There was no reference or control sample as a loop design was used. Each of the 48 samples are represented separately.

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Analysis of sexually dimorphic accumulation of taxoids identifies a female-specific MYB-bHLH complex involved in the paclitaxel biosynthesis of Taxus media

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