Homo sapiens
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PROVIDER: PRJNA261895 | ENA |
REPOSITORIES: ENA
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Project description:We found that MCF7 and ZR751 Sox2-expressing breast cancer cell lines comprise of cells with heterogeneous Sox2 transcription activity reporter response. A small subset of Sox2 reporter responsive cells are more tumourigenic than the bulk Sox2 reporter unresponsive cells. We questioned whether Sox2 exhibit differential gene promoter occupancies in the two cell subsets to govern differential gene expression patterns. Sox2 ChIP in reporter unresponsive (RU) and reporter responsive (RR) cells (duplicate samples) were compared. IgG ChIP in RU and RR cells served as the negative controls.
2014-09-25 | E-GEOD-61703 | biostudies-arrayexpress
Project description:We found that MCF7 and ZR751 Sox2-expressing breast cancer cell lines comprise of cells with heterogeneous Sox2 transcription activity reporter response. A small subset of Sox2 reporter responsive cells are more tumourigenic than the bulk Sox2 reporter unresponsive cells. We questioned whether Sox2 exhibit differential gene promoter occupancies in the two cell subsets to govern differential gene expression patterns.
2014-09-25 | GSE61703 | GEO
Project description:Nectin-4 or PVRL4 is a promising therapeutic target because its augmented expression has been found in a wide range of human cancers. It is of note that Enfortumab Vedotin, an ADC for PVRL4 is clinically used for the treatment of urothelial bladder cancer. In addition, rMV-SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through an interaction with PVRL4. Although the transcripts of PVRL4 are elevated in breast, lung and ovarian cancer, the mechanism(s) of its overexpression has not been uncovered. To clarify the regulatory mechanism(s) of its elevated expression in breast cancer cells, we searched for its regulatory region(s) using ATAC-seq and ChIP-seq data. Using breast cancer cells, we identified an enhancer region. Additional analyses disclosed that FOS interacted with the enhancer region, and the alterations of the FOS-binding motifs decreased the reporter activity. Consistent with these data, exogenous expression of FOS enhanced not only the reporter activity but also PVRL4 expression in breast cancer cells. Furthermore, RNA-seq analysis using breast cancer cells treated with PVRL4-siRNA revealed its possible involvement in cytokine response and immune systems. These data suggest that FOS is involved, at least partly, in the regulation of PVRL4 expression in breast cancer cells, and that elevated PVRL4 expression may regulate response of the cancer cells to cytokines and immune systems.
2023-08-10 | GSE240039 | GEO
Project description:Nectin-4 or PVRL4 is a promising therapeutic target because its augmented expression has been found in a wide range of human cancers. It is of note that Enfortumab Vedotin, an ADC for PVRL4 is clinically used for the treatment of urothelial bladder cancer. In addition, rMV-SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through an interaction with PVRL4. Although the transcripts of PVRL4 are elevated in breast, lung and ovarian cancer, the mechanism(s) of its overexpression has not been uncovered. To clarify the regulatory mechanism(s) of its elevated expression in breast cancer cells, we searched for its regulatory region(s) using ATAC-seq and ChIP-seq data. Using breast cancer cells, we identified an enhancer region. Additional analyses disclosed that FOS interacted with the enhancer region, and the alterations of the FOS-binding motifs decreased the reporter activity. Consistent with these data, exogenous expression of FOS enhanced not only the reporter activity but also PVRL4 expression in breast cancer cells. Furthermore, RNA-seq analysis using breast cancer cells treated with PVRL4-siRNA revealed its possible involvement in cytokine response and immune systems. These data suggest that FOS is involved, at least partly, in the regulation of PVRL4 expression in breast cancer cells, and that elevated PVRL4 expression may regulate response of the cancer cells to cytokines and immune systems.
2023-07-31 | GSE236275 | GEO
Project description:The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. Transcription factor TFAP2C plays a critical role in the regulation of both estrogen receptor-alpha (ERM-NM-1) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines representing different clinical phenotypes. Comparing the genomic binding sites for TFAP2C in the various cell lines, we identified that glutathione peroxidase (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene. Knock-down of TFAP2C, but not the related factor TFAP2A, resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity correlated with endogenous GPX1 expression, and overexpression of exogenous GPX1 induced GPX activity and significantly increased resistance to tert-butyl hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where GPX1 promoter methylation was associated with gene silencing, treatment with 5-aza-dC (an inhibitor of DNA methylation) resulted in activation of GPX1 RNA and protein expression. Methylation of the GPX1 promoter was identified in approximately 20% of primary breast cancers and a highly significant correlation between TFAP2C and GPX1 expression was confirmed when considering only those tumors with an unmethylated promoter, whereas the related factor, TFAP2A, failed to demonstrate a correlation. The results demonstrate that TFAP2C regulates the expression of GPX1, which influences the redox state and sensitivity to oxidative stress induced by peroxides. Given the established role of GPX1 in breast cancer, the results provide an important mechanism for TFAP2C to further influence oncogenesis and progression of breast carcinoma cells. 4 ChIP-Seq data for TFAP2C in human breast carcinoma cell lines MCF-7, BT-474, MDA-MB-453 and SKBR-3.
2012-09-12 | E-GEOD-36351 | biostudies-arrayexpress
Project description:Genes are often activated by enhancers located at large genomic distances. The importance of this positioning is poorly understood. Here, by relocating different promoter-reporter constructs into >1,000 alternative positions within a single locus, we dissected the positional relationship between the mouse Sox2 gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape, in which the native Sox2 gene occupies an optimal position for its activation. Deletion of the gene relaxes this confinement and broadly increases reporter activity. Surprisingly, this confining effect of the Sox2 gene on reporter activity is partially conferred by its ~1 kb coding region. Our local relocation approach provides high-resolution functional maps of a genomic locus and reveals that a gene can strongly constrain its enhancer’s realm of influence.
2024-08-19 | GSE274893 | GEO
Project description:Genes are often activated by enhancers located at large genomic distances. The importance of this positioning is poorly understood. Here, by relocating different promoter-reporter constructs into >1,000 alternative positions within a single locus, we dissected the positional relationship between the mouse Sox2 gene and its distal enhancer. This revealed an intricate, sharply confined activation landscape, in which the native Sox2 gene occupies an optimal position for its activation. Deletion of the gene relaxes this confinement and broadly increases reporter activity. Surprisingly, this confining effect of the Sox2 gene on reporter activity is partially conferred by its ~1 kb coding region. Our local relocation approach provides high-resolution functional maps of a genomic locus and reveals that a gene can strongly constrain its enhancer’s realm of influence.
2024-08-19 | GSE274894 | GEO
Project description:The MCF7 cell line represents a typical epithelial cell line and corresponds to luminal A breast cancer (estrogen-responsive). Overexpression of HAX1 was demonstrated in MCF7 cell line as well as in breast cancer samples, suggesting a role of HAX1 in breast cancer progression. HAX1 is a 32-kDa protein of unknown structure, involved in the regulation of apoptosis, cell migration and calcium homeostasis. It was also shown to bind mRNA. Scarcity of structural elements and the presence of a disordered region, inferred from HAX1 sequence, suggests that HAX1 is intrinsically disordered, and may have many protein-protein interactions. So far about 40 different proteins were characterized as HAX1 protein partners. In the present work, applying immunoaffinity chromatography coupled with mass spectrometry, we identified new candidates for HAX1 binding partners in breast cancer cells. Newly identified proteins may be divided into three, partially overlapping groups: cytoskeleton-associated proteins, GTP-ase associated proteins and RNA-binding proteins. These results imply that HAX1 has more protein partners than hitherto described. Subsequent analysis of these interactions may shed some light into molecular mechanisms of HAX1 functions.
2019-11-14 | PXD007888 | Pride
Project description:The glucocorticoid receptor (GR) binds the human genome at >10,000 sites, but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter- gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs, and may therefore play a major role in driving gene activation in response to GCs. Glucoroticoid receptor binding site chip-seq libraries were cloned into STARR-seq for massively parallel functional analysis. The results were confirmed by ChIP-Exo performed on the GR in A549 cells treated with 100 nM dexamethasone for one hour. This dataset [2] contains the sequences obtained from plasmids transfected into A549 cells isolated from the nuclei of cells treated with DEX or ETOH. [2] contains the abundance of plasmids that cover same overall region as [1], but were not redundant with the content of [1] and were generated in independent experimental steps.
2016-08-25 | E-GEOD-79425 | biostudies-arrayexpress
Project description:BACKGROUND: The AP2 transcription factor family is a set of developmentally regulated, retinoic acid (RA) inducible genes, which regulate expression of estrogen receptor-alpha (ERalpha) in breast carcinoma. We hypothesized that AP2 factors regulate a set of genes characteristic of the hormone responsive breast cancer phenotype. To better understand the role of AP2 factors in hormone responsive breast cancer, we sought to identify AP2-target genes in breast epithelial cells. MATERIALS AND METHODS: Overexpression of AP2 factors was achieved in human mammary epithelial cells (HMECs) using adenoviral vectors. AP2 target genes were identified by comparative hybridization to cDNA microarrays containing 30,000 human genes. Expression patterns were confirmed by Northern and Western blot and by elimination of AP2 using siRNA. Potential regulatory elements in promoters of target genes were identified by DNase I hypersensitive site mapping. : Comparative cDNA microarray hybridization identified a set of genes induced by overexpression of AP2alpha and AP2gamma in HMECs. The up-regulation of cellular retinoic acid-binding protein 2 (CRABPII), EST-1, and ECM1 was induced by overexpression of AP2alpha, AP2gamma, or a chimeric AP2 factor in which the activation domain of AP2alpha was replaced by the activation domain of herpesvirus VP16. Interestingly, hormone unresponsive MDA-MB-231 cells were resistant to CRABPII induction by any of the AP2 factors. Elimination of AP2gamma in MCF7 cells resulted in a significant reduction in CRABPII expression. AP2alpha induced DNase I hypersensitive sites in the promoter of the CRABPII gene at -5000 bp, which corresponds to the site of action of RAR/RXR factors. CONCLUSIONS: AP2 factors regulate CRABPII expression in HMECs and breast cancer cells and accounts for the associated expression of ERalpha and CRABPII in hormone responsive breast cancer. Because CRABPII mediates growth suppressive effects of RA in breast cancer, the data suggest that AP2 factors have the ability to mediate RA responsiveness through the regulation of CRABP II expression. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2007-08-09 | E-GEOD-7616 | biostudies-arrayexpress