Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with anti-CD3/CD28 from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.
Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with antiCD3/CD28 from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.
Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with anti-CD3/CD28 from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.
Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of autoantigen specific CD4+ T cells from XX and XY- mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.
Project description:To determine the role of sex chromsomes in sex differences of autoimmune disease, we used high throughput RNA sequencing to analyze the transciptomes of CD4+ T cells stimuated with antiCD3/CD28 from XXSry and XY-Sry mice using the “four core genotypes” mouse model. We found higher expression of several X genes in the XY- genotype compared to XX, suggesting a difference in DNA methylation of these genes between Xp and Xm. In a hypothesis driven targeted approach, we investigated two immunomodulatory X genes, Tlr7 and FoxP3 and found that the promoter regions of both genes had more DNA methylation on the Xp than Xm, and that both genes had higher expression in autoantigen stimulated CD4+ T cells from XY- compared to XX mice. This study provides new insights regarding how sex chromsomes affect gene expression and cause sex differences in autoimmune disease.
Project description:Sex chromosome dosage differences between males and females are a significant form of natural genetic variation in many species. Like many species with chromosomal sex determination, Drosophila females have two X chromosomes, while males have one X and one Y. The model species D. melanogaster has five roughly equally sized chromosome arms, one of which is the X chromosome. However, fusions of sex chromosomes with autosomes have occurred along the lineage leading to D. pseudoobscura and D. miranda. The resulting neo-sex chromosomes are gradually evolving the properties of sex chromosomes, and neo-X chromosomes are becoming targets for the molecular mechanisms that compensate for differences in X chromosome dose between sexes. We have previously shown that D. melanogaster possess at least two dosage compensation mechanisms: the well- characterized MSL-mediated dosage compensation active in most somatic tissues, and another system active during early embryogenesis prior to the onset of MSL-mediated dosage compensation. To better understand the developmental constraints on sex chromosome gene expression and evolution, we sequenced mRNA from individual male and female embryos of D. pseudoobscura and D. miranda, from ~0.5 to 8 hours of development. Autosomal expression levels are highly conserved between these species. But, unlike D. melanogaster, we observe a general lack of dosage compensation in D. pseudoobscura and D. miranda prior to the onset of MSL-mediated dosage compensation. The extent of female bias on the X chromosomes decreases through developmental time with the establishment of MSL-mediated dosage compensation, but may do so more slowly in D. miranda than D. pseudoobscura. Thus either there has been a lineage-specific gain or loss in early dosage compensation mechanism(s), or increasing X chromosome dose may strain dosage compensation systems and make them less effective. These results also prompt a number of questions about whether species with more sex-linked genes have more sex-specific phenotypes, and how much transcript level variance is tolerable during critical stages of development.
Project description:Sex chromosomes and more particularely the X chromosomes are known to have a major effect on hybrid male sterility. In this experiment by making use of the reciprocal hybrids between D. simulans and D. sechellia, we are showing the effect of these chromosomes on gene expression in male hybrids Keywords: X chromosome, hybrid