Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA91291 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease characterized by alveolar epithelial cell type II (AECII) injury and enhanced fibroblast/myofibroblast proliferation. Recent data show that maladaptive endoplasmic reticulum (ER)-stress leading to AECII apoptosis could play a key role in IPF, although it is still unclear how precisely such response is initiated and signalled. C/EBP homologous protein (CHOP) has been suggested to contribute to a maladaptive ER-stress response in general and has been found to be induced and to be translocated into the nucleus of AECII in IPF in particular. We here show for the first time a novel mechanism for the regulation of CHOP expression during ER-stress in AECII via AP-1 and c-Ets-1. We found these two transcription factors to be up-regulated in AECII under ER-stress conditions and to interact with each other to jointly bind to the CHOP promoter, thereby inducing CHOP gene expression. Moreover, we show for the first time that singular CHOP overexpression in vitro and in vivo is indeed capable of inducing apoptosis of AECII and, consequently, lung fibroblast proliferation and up-regulation of pro-fibrotic markers. We therefore believe that CHOP plays a key role in AEC injury and consecutive fibrosis.
2017-09-23 | GSE87298 | GEO
Project description:We report the direct target genes of ATF4 and CHOP in response to endoplasim reticulum stress through next generation sequencing. By obtaining genowide sequence from chromatin immunoprecipitated DNA with anti-CHOP and anit-ATF4, we identified direct binding sites of ATF4 and CHOP in promoter regions of their target genes in mouse embrynic fibroblasts (MEFs) in response to ER stress. In addition, we obtained list of genes which are differentially regulated in Atf4 or Chop-deficient MEFs compared to the wild-type MEFs in response to ER stress. We found that genes related with unfolded protein response and protein synthesis were directly regulated by ATF4 and CHOP. Through this observation, we conclude that main role of ATF4 and CHOP as transcription factors is to enhance mRNA translation in respone to ER stress. This sutdy provide new insight of genetic network of ATF4 and CHOP in response to ER stress. For ChIP-seq, Chop+/+ and Chop-/- MEFs were treated with Tunicamycin, N-glycosylation inhibitor, to induce ER stress for 8hr. Atf4+/+ and Atf4-/- MEFs were also treated same condition for ChIP-Seq. For mRNA-seq, wild-type, Atf4-/-, and Chop-/- MEFs were treated with tunicamycin for 8hr for experiments.
2013-04-11 | E-GEOD-35681 | biostudies-arrayexpress
Project description:HAMLET triggers a p38- and ER stress-dependent death response in carcinoma cells. Transcriptome and proteome analysis detected an increase in p38 expression and phosphorylation exclusively in carcinoma cells and p38 inhibitors delayed the death response to HAMLET in carcinoma and lymphoma cells. ER stress gene expression was also increased in tumor cells and HAMLET triggered rapid XBP1 mRNA splicing, eIF2a phosphorylation, and ATF6 cleavage as well as Hsc70 and CHOP activation, suggesting that ER stress caused by HAMLET may trigger p38 phosphorylation and death. The p38 inhibitor reduced the transcription of both p38 and ER stress gene transcription. Healthy differentiated cells, in contrast, showed no alteration in p38 signaling but a rapid innate immune response was detected and the cells survived HAMLET challenge. 2 cell lines, time course, HAMLET treatment
2010-08-24 | E-GEOD-23772 | biostudies-arrayexpress
Project description:Primary mouse embryonic fibroblasts (pass 3 to 4) were treated with tunicamycin (2 micrograms/ml) for specified times - genotypes were WILDTYPE and CHOP-/-. Each time point n=4. C/EBP homologous protein CHOP is activated by ER stress, and CHOP deletion protects against its lethal consequences.
2007-12-11 | E-GEOD-2082 | biostudies-arrayexpress
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.
| S-EPMC8784167 | biostudies-literature
Project description:We report the direct target genes of ATF4 and CHOP in response to endoplasim reticulum stress through next generation sequencing. By obtaining genowide sequence from chromatin immunoprecipitated DNA with anti-CHOP and anit-ATF4, we identified direct binding sites of ATF4 and CHOP in promoter regions of their target genes in mouse embrynic fibroblasts (MEFs) in response to ER stress. In addition, we obtained list of genes which are differentially regulated in Atf4 or Chop-deficient MEFs compared to the wild-type MEFs in response to ER stress. We found that genes related with unfolded protein response and protein synthesis were directly regulated by ATF4 and CHOP. Through this observation, we conclude that main role of ATF4 and CHOP as transcription factors is to enhance mRNA translation in respone to ER stress. This sutdy provide new insight of genetic network of ATF4 and CHOP in response to ER stress.
2013-04-11 | GSE35681 | GEO