Project description:To understand the mechanisms through which JunB regulates Tregs-mediated immune regulation, we examined the global gene expression profiles in the JunB WT and KO Tregs by performing RNA sequencing (RNA-seq) analysis.
Project description:Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Here, we show NM1 has a global role in chromatin regulation and this likely impacts global transcription. High-content phenotypic profiling and transcriptional profiling by RNA-Seq on NM1 KO mouse embryonic fibroblasts show extensive chromatin alteration and differential gene expression compared to a WT condition. In particular, NM1 deletion leads to significant upregulation of genes involved in DNA damage response and cell cycle, which is further supported by increased DNA damage revealed by increased γ-H2AX foci number and proliferation rate. We found that upon DNA damage, NM1 directly regulates expression of Cdkn1A (p21) and binds to p53. NM1 recruits histone acetyl-transferase PCAF and histone methyl-transferase Set1 to p21 promoter for histone H3 acetylation and methylation, facilitating Cdkn1A gene transcription. We propose that NM1 regulates the transcriptional response upon DNA damage and imply an involvement for NM1 in genome stability.
Project description:Plasma membrane tension is an important feature that determines the cell shape and influences processes such as cell motility, spreading, endocytosis and exocytosis. Unconventional class 1 myosins are potent regulators of plasma membrane tension because they physically link the plasma membrane with the adjacent cytoskeleton. We identified nuclear myosin 1 (NM1) - a putative nuclear isoform of myosin 1c (Myo1c) - as a new player in the field. Although having specific nuclear function, we show that NM1 localizes preferentially to the plasma membrane. Deletion of NM1 causes more than 50% increase in the elasticity of the plasma membrane around the actin cytoskeleton as measured by atomic force microscopy. This higher elasticity of NM1 knock-out cells leads to 25% higher resistance to short-term hypotonic environment and rapid cell swelling. In contrary, overexpression of NM1 in WT cells leads to additional 30% reduction of their survival. We have brought evidence that NM1 has a direct functional role in the cytoplasm as a dynamic linker between the cell membrane and the underlying cytoskeleton, regulating the degree of effective plasma membrane tension. We used tissues from NM1 WT and KO mice with highest expression of NM1, lungs and heart (3 replicates each) and skin fibroblast derived from each mice (2 replicates each)
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:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
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.