Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA177603 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Multiple cancer-associated single nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500 kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer- related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo. Exon-array analysis of mouse colon tissues from Myc-335 null and wild-type mouse (both mice are male and from the same litter). Related ChIP-seq data available in Short Read Archive, Accession ERP001919
2012-11-02 | E-GEOD-41219 | biostudies-arrayexpress
Project description:Multiple cancer-associated single nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500 kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer- related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.
2012-11-02 | GSE41219 | GEO
Project description:Analysis of Gene Expression in KO mice lacking the NOTCH1-bound MYC putative enhancer located at +1.43K downstream of the MYC gene. Enrichment of MYC signature genes were analyzed by GSEA. Results show that MYC expression signature is indeed significantly enriched. Conditional Knockout or WT mice were treated with Tamoxifen or Veicle
2014-09-07 | E-GEOD-57988 | biostudies-arrayexpress
Project description:We identified an enhancer element near IGF2 locus that is possibly involved with dopamine function and schizophrenia. A knockout mouse was generated for the enhancer element in the IGF2 locus. We then characterized the striatal synaptosomes ( i.e. biological fraction representing pre- post synaptic nerve terminal)by mass spectometry from WT and Igf2 enhancer KO mice.
2019-05-31 | PXD012786 | Pride
Project description:Analysis of Gene Expression in KO mice lacking the NOTCH1-bound MYC putative enhancer located at +1.43K downstream of the MYC gene. Enrichment of MYC signature genes were analyzed by GSEA. Results show that MYC expression signature is indeed significantly enriched.
2014-09-07 | GSE57988 | GEO
Project description:The transition from castration resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) is emerging as an important mechanism of treatment resistance. NEPC are associated with over-expression and gene amplification of MYCN (encoding N-Myc). N-Myc is a bona fide driver oncogene in several rare tumor types, but its role in prostate cancer progression is not well established. Integrating a novel genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc over-expression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC tumors which includes an abrogation of AR signaling and induction of Polycomb Repressive Complex 2 signaling and that N-Myc interacts with AR and this interaction depends on Enhancer of Zeste Homolog 2. Altogether, our data shows that N-Myc drives the neuroendocrine phenotype in prostate cancer.
2016-09-08 | GSE86532 | GEO
Project description:Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.
| EGAS00001004808 | EGA
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in developed countries, with extremely limited therapeutic options. MYC is a highly pleiotropic transcription factor with broad biological functions. However, the effect of intestinal MYC on metabolic diseases has not been studied. Here, an unexpected role for intestinal MYC in NAFLD was uncovered. MYC was increased in ileum biopsies from obese people and positively correlated with body-mass index. Intestine-specific reduction of MYC in mice improved high-fat diet (HFD) -induced obesity and hepatic steatosis. Mechanistically, reduced expression of MYC in the intestine promoted glucagon-like peptide-1 (GLP-1) production and secretion via upregulating carbohydrate-responsive element binding protein (ChREBP) and solute carrier family 2, member 2 (GLUT2)/solute carrier family 5, member 1 (SGLT1), respectively. Furthermore, 10058-F4, a MYC inhibitor, had therapeutic effects on HFD-induced metabolic disorders, accompanied by increased GLP-1 and reduced ceramides in the serum. This study highlights intestinal MYC as a putative drug target against NAFLD.
2021-05-10 | GSE155460 | GEO
Project description:Notch is needed for T cell development and is a common oncogenic driver in T cell acute lymphoblastic leukemia. Myc is a critical target of Notch in normal and malignant pre-T cells, but how Notch regulates Myc is unknown. Here, we identify a distal enhancer located >1 Mb 3' of human and murine Myc that binds Notch transcription complexes and physically interacts with the Myc proximal promoter. The Notch1 binding element in this region activates reporter genes in a Notch-dependent, cell context-specific fashion that requires a conserved Notch complex binding site. Acute changes in Notch activation produce rapid changes in H3K27 acetylation across the entire enhancer (a region spanning >600 kb) that correlate with Myc expression. This broad Notch-influenced region is comprised of an enhancer region containing multiple domains, recognizable as discrete H3K27 acetylation peaks. Leukemia cells selected for resistance to Notch inhibitors express Myc despite epigenetic silencing of enhancer domains near the Notch transcription complex binding sites. Notch-independent expression of Myc in resistant cells is highly sensitive to inhibitors of Brd4, a change in drug sensitivity that is accompanied by preferential association of the Myc promoter with more 3’ enhancer domains that are strongly dependent on Brd4 for function. These findings indicate that altered long-range enhancer activity can mediate resistance to targeted therapies and provide a mechanistic rationale for combined targeting of Notch and Brd4 in leukemia.
2014-11-11 | GSE61504 | GEO