Project description:Brachyury (or T) is expressed in the primitive streak, tailbud and notochord of the early mouse embryo (Herrmann et al., 1990; Wilkinson et al., 1990). It plays a key role in early development: mouse embryos lacking functional Brachyury protein fail to gastrulate properly, do not form a differentiated notochord, and lack structures posterior to somite seven (Chesley, 1935; Dobrovolskaïa-Zavadskaïa, 1927; Naiche et al., 2005; Wilson et al., 1995; Wilson et al., 1993; Yanagisawa et al., 1981) We apply a ChIP-on-chip approach to identify targets of Brachyury during mouse ES cell differentiation. ES cells provide an abundant source of differentiating cells and the identification of Brachyury targets in such cells will shed light on the mechanisms of ES cell differentiation and, by analyzing the targets in the developing embryo, will reveal to what extent they provide a bone fide model of early mouse development.
Project description:Brachyury (or T) is expressed in the primitive streak, tailbud and notochord of the early mouse embryo (Herrmann et al., 1990; Wilkinson et al., 1990). It plays a key role in early development: mouse embryos lacking functional Brachyury protein fail to gastrulate properly, do not form a differentiated notochord, and lack structures posterior to somite seven (Chesley, 1935; DobrovolskaM-CM-/a-ZavadskaM-CM-/a, 1927; Naiche et al., 2005; Wilson et al., 1995; Wilson et al., 1993; Yanagisawa et al., 1981) We apply a ChIP-on-chip approach to identify targets of Brachyury during mouse ES cell differentiation. ES cells provide an abundant source of differentiating cells and the identification of Brachyury targets in such cells will shed light on the mechanisms of ES cell differentiation and, by analyzing the targets in the developing embryo, will reveal to what extent they provide a bone fide model of early mouse development. The brachyury IP expts used 3 independent biological replicates hybridised to design 1 and 2 chips per replicate Design 1 raw file AE_251471610189 + Design 2 raw file AE_251471710182 = replicate 1 Design 1 raw file AE_251471610716 + Design 2 raw file AE_251471710724 = replicate 2 Design 1 raw file AE_251471610717 + Design 2 raw file AE_251471710725 = replicate 3 in all cases IP DNA label was Cy5 and whole chromatin Cy3 Design 1 files GSM417692 Design 2 files GSM417704 Isotype control experiment performed 1 x ie design 1 raw file AE_251471610714 design 2 raw file AE_251471710722 in GSM417714 and GSM417756 IP DNA label was Cy5 and whole chromatin Cy3 as for brachyury data
Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.