Project description:ATAC-seq profiling of Nfat5 KO and wild type macrophages derived from bone marrow (primary cells), treated or not with Lipopolysaccharide (LPS).
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.
Project description:The experiment was designed to determine the gene expression changes cultured brown adipocytes in response to the inflammatory stimulus of LPS treatment. Both wild type and TLR4 knockout cells were applied to enable assessment of the contribution of TLR4 to the response.
Project description:Innate immune detection of pathogens by macrophages requires a rapid and large scale mobilisation of cellular resources towards an appropriate immune response, mainly involving altered protein expression. Pathogen recognition is mediated by pattern recognition receptor (PRR) sensing of conserved microbial patterns, a prototypical example being recognition of LPS by TLR4. This leads to induction of pro-inflammatory cytokines, chemokines and type I interferons (IFN Is) which together mobilise appropriate anti-pathogen responses. IFN Is signal to transcription of IFN-stimulated genes (ISG) which encode numerous anti-viral proteins. Many studies have contributed to a detailed understanding of transcriptional regulation of mRNA during such responses, however much less is known about the contribution of protein complexes required for mRNA translation. Here we examine the role of the evolutionarily conserved elongator complex in PRR signaling in macrophages. Elongator modifies tRNAs at U34 to facilitate more efficient wobble interactions between tRNAs and mRNA codons. In macrophages, deletion of Elp3, the catalytic subunit of elongator, led to an impaired PRR-IFN I-ISG signaling axis. The ELP3-dependent LPS-stimulated proteome was enriched with proteins involved in PRR activation of IRFs and in IFN signalling. Specifically, ELP3 was required for expression of key transcription factors regulating this axis, for TYK2-dependent IFN-I signaling and for IRF3 activation for some, but not all, PRRs. Importantly, ELP3 was also necessary for innate immune gene induction following virus infection. These data reveal specific roles for elongator in PRR signaling and illustrate the underappreciated importance of translational regulation in optimal anti-pathogen innate immune responses.