Project description:This SuperSeries is composed of the following subset Series:; GSE826: Aging in heads from adult Drosophila males, w118 strain; GSE827: Oxidative stess in Drosophila heads Experiment Overall Design: Refer to individual Series
Project description:We explored the microevolutionary trends of CTCF binding evolution by preforming ChIP-seq experiments in five closely related Mus strains, subspecies and species: Mus musculus domesticus, Mus musculus castaneus, Mus spretus, Mus caroli and Mus pahari. All experiments were performed in adult male liver samples in 3 biological replicates and with an input control set. Complementary RNA-seq data from this same study have been deposited in ArrayExpress under accession numebr E-MTAB-5768 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5768 ).
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. Keywords: multi-species comparison
Project description:LSH/DDM1 enzymes are required for DNA methylation in higher eukaryotes and have poorly defined roles in genome maintenance in yeast, plants, and animals. The filamentous fungus Neurospora crassa is a tractable system that encodes a single LSH/DDM1 homolog (NCU06306). We report that the Neurospora LSH/DDM1 enzyme is encoded by mutagen sensitive-30 (mus-30), a locus identified in a genetic screen over 25 years ago. We show that MUS-30-deficient cells have normal DNA methylation, but are hypersensitive to the DNA damaging agent MMS (methyl methanesulfonate). MUS-30 is a nuclear protein, consistent with its predicted role as a chromatin remodeling enzyme, and levels of MUS-30 are increased following DNA damage. MUS-30 co-purifies with Neurospora WDR76, a homolog of yeast Changed Mutation Rate-1 and mammalian WD40 repeat domain 76. Deletion of wdr76 rescued MMS-hypersensitivity of Dmus-30 strains, demonstrating that the MUS-30-WDR76 interaction is functionally important. DNA damage-sensitivity of Dmus-30 is also partially suppressed by deletion of methyl adenine glycosylase-1, a component of the base excision repair machinery (BER); however, the rate of BER is not affected in Dmus-30 strains. It was reported that mammalian LSH is required for efficient double strand break (DSB) repair. We found that MUS-30-deficient cells were not defective for DSB repair, and we observed a negative genetic interaction between Dmus-30 and Dmei-3, the Neurospora RAD51 homolog required for homologous recombination. These data are consistent with a role for MUS-30 that is independent of DSB repair. Our findings demonstrate that LSH/DDM1 enzymes are key regulators of genome stability in eukaryotes. crf5-1 isolates (two replicates each from the F1 and F2 generation) were grown in Vogel's minimal medium for 48 hours. As a control, two replicates of the wildtype strain were grown under identical conditions.
Project description:We analyzed KDM1A (LSD1) occupancy in the Xi during somatic cell reprogramming of female mouse cells. We use MEFs from hybrid embryos by crossing male Mus spretus and female Mus musculus domesticus C57BL/6J to distiguish genome DNA from the Xi. We found a possible physical and/or functional regulation of KDM1A during the X chromosome reactivation in the intiation site on the Xi.
Project description:Here, we mapped cell-type specific chromatin domain organization in adult mouse cerebral cortex and report strong enrichment of Endogenous Retrovirus 2 (ERV2) repeat sequences in the neuron-specific heterochromatic 'B2NeuN+' megabase-scaling subcompartment. Comparative chromosomal conformation mapping in Mus spretus and Mus musculus revealed neuron-specific reconfigurations tracking recent ERV2 retrotransposon expansions in the murine germline, with significantly higher B2 megadomain contact frequencies at sites with ongoing ERV2 insertions in Mus musculus. Ablation of the retrotransposon silencer Kmt1e/Setdb1 (KO) triggered B2 megadomain disintegration and rewiring with open chromatin domains enriched for cellular stress response genes, along with severe neuroinflammation and proviral assembly of ERV2/Intracisternal-A-Particles (IAPs) infiltrating dendrites and spines. We conclude that neuronal megadomain architectures include evolutionarily adaptive heterochromatic organization which, upon perturbation, unleashes ERV proviruses with strong tropism within mature neurons.
Project description:LSH/DDM1 enzymes are required for DNA methylation in higher eukaryotes and have poorly defined roles in genome maintenance in yeast, plants, and animals. The filamentous fungus Neurospora crassa is a tractable system that encodes a single LSH/DDM1 homolog (NCU06306). We report that the Neurospora LSH/DDM1 enzyme is encoded by mutagen sensitive-30 (mus-30), a locus identified in a genetic screen over 25 years ago. We show that MUS-30-deficient cells have normal DNA methylation, but are hypersensitive to the DNA damaging agent MMS (methyl methanesulfonate). MUS-30 is a nuclear protein, consistent with its predicted role as a chromatin remodeling enzyme, and levels of MUS-30 are increased following DNA damage. MUS-30 co-purifies with Neurospora WDR76, a homolog of yeast Changed Mutation Rate-1 and mammalian WD40 repeat domain 76. Deletion of wdr76 rescued MMS-hypersensitivity of Dmus-30 strains, demonstrating that the MUS-30-WDR76 interaction is functionally important. DNA damage-sensitivity of Dmus-30 is also partially suppressed by deletion of methyl adenine glycosylase-1, a component of the base excision repair machinery (BER); however, the rate of BER is not affected in Dmus-30 strains. It was reported that mammalian LSH is required for efficient double strand break (DSB) repair. We found that MUS-30-deficient cells were not defective for DSB repair, and we observed a negative genetic interaction between Dmus-30 and Dmei-3, the Neurospora RAD51 homolog required for homologous recombination. These data are consistent with a role for MUS-30 that is independent of DSB repair. Our findings demonstrate that LSH/DDM1 enzymes are key regulators of genome stability in eukaryotes.
Project description:Stress leads to important adaptive physiological responses including release of catecholamine from the adrenal medulla. Repeated or prolonged stess increses the propensity for many disorders including cardiovascular disease and neuropsychiatric disorders. The susceptibility to stress is determined by a number of factors including prior experience with stress. It has been found that while there is adaptation to prolonged cold stres; it leads to sensitization when cold stressed animals are exposed to a different (novel) stressor. Our study aims to determine the mechanis of this adaptatio and sensitization. We will determine teh gene expression patterns in rat adrenal medulla in response to severa times of cold stress. We will also determine the changes in gene expresion with single immobilization stress in adrenal medulla of rat with an dwithout preexposure to cold stress to investigate the mechanism of sensitizatio in cold adapted animals. We hypothesize that during the course of cold stess there are alterations in gene expression of several neurotransmitter related genes and transcription factors. In expression of several trascription factors, such as Fra-2 which lead to an exaggerated response to teh novel stresor. Rats were exposed to cold stress (4 degree C) for 1, 7, or 28 days. A parallel group was kept at room temperature (unstressed). Unstressed or rats preexposed to 28 days cold were immobilized for 2 hrs and killed by decapitation. The adrenal medullae, separatedly from right and left side, have been dissected and individually frozen at - 70 degree C. We will pool samples from 4 rats per treatment to control for variability.
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. The design we employed is a reference design. All tissues were hybridized against a pool of that same tissue from 9 C57BL6 mice. All mice were roughly 12 weeks of age. To control for biological variation, we have used several individual males from each sub-species. RNA was isolated from three different organs, namely brain, liver/kidney and testis.