Characterization of nucleolus-associated domains in mus musculus and their dynamics after inactivation of the Upstream binding factor protein
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE80441 | GEO | 2018/02/02
REPOSITORIES: GEO
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Project description:Nucleolus plays a key role in organizing global nuclear structure and facilitating gene regulation, but the three dimensional information within the nucleolus associated chromatins are still unknown, so here we development the Nucleolus Hi-C (NHi-C) experimental technique, which combines the nucleolus isolation with Hi-C experiment, and study the interactions within and surrounding nucleolus in human cells with a high resolution. With NHi-C experiment, we report how the nucleolus-associated chromatin regions interact at genome scale, and how these interactions organize the repressive nucleus architecture.
2021-02-01 | GSE90003 | GEO
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.
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Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
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Project description:BACKGROUND:The molecular pathways involved in the transition from uterine quiescence to overt labour are mapped and form the currently established pharmacological targets for both the induction and inhibition of human labour. However, both spontaneous premature labour and functional dystocia occur and are difficult to treat adequately. The identification of upstream regulators involved in the onset and orchestration of labour pathways is essential to develop additional therapies that will contribute to the regulation of the timing of birth. OBJECTIVES:To define uterine biological processes and their upstream activators involved in the transition from uterine quiescence to overt labour. STUDY DESIGN:The uterus of non-pregnant and pregnant FVB M. musculus is collected at embryonic days (E) 6.5, 8.5, 10.5, 12.5, 15.5 and 17.5 and the uterine transcriptome is determined using the Illumina mouse Ref8v2 micro-array platform. K-means clustering and Ingenuity Pathway Analysis are applied to further dissect the transcriptome data. RESULTS:From E6.5 to E17.5, 5405 genes are significantly differentially expressed and they segregate into 7 unique clusters. Five of the 7 clusters are enriched for genes involved in specific biological processes that include regulation of gene-expression, T-cell receptor activation, Toll-like receptor signalling and steroid metabolism. The identification of upstream activators for differentially expressed genes between consecutive time points highlights the E10.5 to E12.5 window during which the role from progesterone switches from an activated state to the inhibited state reflecting the process of functional progesterone withdrawal essential for the transgression from myometrial quiescence to synchronized contractions. For this time window in which 189 genes are differentially expressed we define 22 putative upstream activators of which NUPR1 and TBX2 are the most significant with respectively an activated and an inhibited status. CONCLUSIONS:Gene expression profiling of mice uterus from E6.5 to E17.5 results in 7 unique gene expression clusters from early to late pregnancy that define the landscape of molecular events in ongoing pregnancy. In the current dataset progesterone is predicted as an activated upstream regulator and maintainer of myometrial quiescence and is active till E10.5. Progesterone is predicted as an inhibited upstream regulator at E12.5. We identify 22 upstream regulators in the E10.5 to E12.5 time window where the switch to progesterone withdrawal occurs. They are putative relevant upstream activators of labour.
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Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
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Project description:BackgroundLong terminal repeat (LTR) retrotransposons make up a large fraction of the typical mammalian genome. They comprise about 8% of the human genome and approximately 10% of the mouse genome. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function. Recent advances in genome sequencing of a variety of model organisms has provided an unprecedented opportunity to evaluate better the diversity of LTR retrotransposons resident in eukaryotic genomes.ResultsUsing a new data-mining program, LTR_STRUC, in conjunction with conventional techniques, we have mined the GenBank mouse (Mus musculus) database and the more complete Ensembl mouse dataset for LTR retrotransposons. We report here that the M. musculus genome contains at least 21 separate families of LTR retrotransposons; 13 of these families are described here for the first time.ConclusionsAll families of mouse LTR retrotransposons are members of the gypsy-like superfamily of retroviral-like elements. Several different families of unrelated non-autonomous elements were identified, suggesting that the evolution of non-autonomy may be a common event. High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.
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Project description:House mice (Mus musculus) emit ultrasonic vocalizations (USVs), which are surprisingly complex and have features of bird song, but their functions are not well understood. Previous studies have reported mixed evidence on whether there are sex differences in USV emission, though vocalization rate or other features may depend upon whether potential receivers are of the same or opposite sex. We recorded the USVs of wild-derived adult house mice (F1 of wild-caught Mus musculus musculus), and we compared the vocalizations of males and females in response to a stimulus mouse of the same- or opposite-sex. To detect and quantify vocalizations, we used an algorithm that automatically detects USVs (Automatic Mouse Ultrasound Detector or A-MUD). We found high individual variation in USV emission rates (4 to 2083 elements/10 min trial) and a skewed distribution, with most mice (60%) emitting few (≤50) elements. We found no differences in the rates of calling between the sexes overall, but mice of both sexes emitted vocalizations at a higher rate and higher frequencies during opposite- compared to same-sex interactions. We also observed a trend toward higher amplitudes by males when presented with a male compared to a female stimulus. Our results suggest that mice modulate the rate and frequency of vocalizations depending upon the sex of potential receivers.
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Project description:Nucleolus-associated DNA was isolated from cross-linked proliferating and senescent IMR90 human fibroblasts and hybridized against genomic (1) or non-nucleolar (2) DNA to map nucleolus-associated chromosomal domains.
2017-06-18 | GSE78043 | GEO
Project description:Global analysis of gene expression in MEF cells and villi enterocytes expressing SV40 T antigens
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