TFAP2C regulates multiple pathways of estrogen signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE8640 | GEO | 2007/12/17
SECONDARY ACCESSION(S): PRJNA101825
REPOSITORIES: GEO
Similar Datasets
Project description:We were interested in determining what genes might be controlled by TFAP2C and/or TFAP2A, either directly or indirectly through regulation of ER-alpha and potentially other signaling pathways. We performed an microarray analysis in MCF7 cells with elimination of either TFAP2C or TFAP2A. The patterns of gene expression with alteration of TFAP2 activity were compared to changes in expression induced by estrogen exposure. Knock-down of TFAP2C in the presence of estrogen altered the pattern of several known ERalpha-regulated genes and a number of genes outside the estrogen-regulated pathways. Experiment Overall Design: 6 samples were analyzed. Experiment Overall Design: 1. MCF7 cells treated with TFAP2C siRNA, without the presence of estrogen. Experiment Overall Design: 2.MCF7 cells treated with TFAP2C siRNA, with the presence of estrogen. Experiment Overall Design: 3.MCF7 cells treated with TFAP2A siRNA, without the presence of estrogen. Experiment Overall Design: 4.MCF7 cells treated with TFAP2A siRNA, with the presence of estrogen. Experiment Overall Design: 5.MCF7 cells with no siRNA treatment, without the presence of estrogen. Experiment Overall Design: 6.MCF7 cells with no siRNA treatment, with the presence of estrogen.
2008-06-16 | E-GEOD-8640 | biostudies-arrayexpress
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:We have genetically ablated the neural crest by simultaneously knocking out tfap2a and tfap2c in developing zebrafish embryos. We have collected 10 single embryos at the 15 somites stage from all nine possible genotypic combinations which can be found when heterozygous parent carriers of tfap2a and tfap2c are crossed. Embryos were prepped in singular, barcoded and RNA-Seq libraries were created using True-Seq stranded RNA-Seq LT kit. Libraries were paired end sequenced at 75bp on an Illumina Hi-Seq 2500.
2018-05-01 | E-MTAB-6106 | biostudies-arrayexpress
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 (ERα) 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.
2012-09-12 | GSE36351 | GEO
Project description:In developing melanocytes and in melanoma cells, multiple paralogs of the Activating-enhancer-binding Protein 2 family of transcription factors (TFAP2) contribute to expression of genes encoding pigmentation regulators, but their interaction with Microphthalmia transcription factor (MITF), a master regulator of these cells, is unclear. Supporting the model that Tfap2 facilitates MITF's ability to activate expression of pigmentation genes, single-cell seq analysis of zebrafish embryos revealed that pigmentation genes are only expressed in the subset of mitfa-expressing cells that also express Tfap2 paralogs. To test this model in SK-MEL-28 melanoma cells we deleted the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C, creating TFAP2 knockout (TFAP2-KO) cells. We then assessed gene expression, chromatin accessibility, binding of TFAP2A and of MITF, and the chromatin marks H3K27Ac and H3K27Me3 which are characteristic of active enhancers and silenced chromatin, respectively. Integrated analyses of these datasets indicate TFAP2 paralogs directly activate enhancers near genes enriched for roles in pigmentation and proliferation, and directly repress enhancers near genes enriched for roles in cell adhesion. Consistently, compared to WT cells, TFAP2-KO cells proliferate less and adhere to one another more. TFAP2 paralogs and MITF co-operatively activate a subset of enhancers, with the latter necessary for MITF binding and chromatin accessibility. By contrast, TFAP2 paralogs and MITF do not appear to co-operatively inhibit enhancers. These studies reveal a mechanism by which TFAP2 profoundly influences the set of genes activated by MITF, and thereby the phenotype of pigment cells and melanoma cells.
2022-04-26 | GSE190610 | GEO
Project description:This study is an attempt to characterize the molecular basis for the functional differences between TFAP2A and TFAP2C. Recent findings have highlighted a critical role for the TFAP2C (AP-2M-NM-3) transcription factor in maintaining the luminal phenotype through the regulation of luminal-associated genes. Of particular interest is that the highly homologous AP-2 family member, TFAP2A (AP-2M-NM-1), is expressed in luminal breast cancer but appears to have a functionally distinct role in gene regulation. There is 83% similarity between TFAP2A and TFAP2C with 76% identity in the carboxyl-half of the proteins containing the DNA binding and dimerization domains. Although the two family members appear to have complementary and overlapping roles in regulating neural crest development, they have clear functional differences with regard to regulation of ERM-NM-1 expression. The global genomic binding pattern for TFAP2A and TFAP2C is highly similar. Genomic binding for TFAP2A and TFAP2C in the regulatory region for luminal-associated genes further demonstrated co-localization of the two factors. On the other hand, clear functional differences exist when comparing the effect on the pattern of gene expression following knockdown of TFAP2A vs. TFAP2C. In each case, knockdown of TFAP2C resulted in an abrogation of expression (RNA and protein) of the luminal-associated gene, whereas, knockdown of TFAP2A had minimal or no effect. By contrast, a known TFAP2A target gene, CDKN1A, was responsive to TFAP2A only. 1 ChIP-Seq data for TFAP2A in human breast carcinoma cell line MCF-7. See associated publication.
2014-04-12 | E-GEOD-44257 | biostudies-arrayexpress
Project description:This study is an attempt to characterize the molecular basis for the functional differences between TFAP2A and TFAP2C. Recent findings have highlighted a critical role for the TFAP2C (AP-2γ) transcription factor in maintaining the luminal phenotype through the regulation of luminal-associated genes. Of particular interest is that the highly homologous AP-2 family member, TFAP2A (AP-2α), is expressed in luminal breast cancer but appears to have a functionally distinct role in gene regulation. There is 83% similarity between TFAP2A and TFAP2C with 76% identity in the carboxyl-half of the proteins containing the DNA binding and dimerization domains. Although the two family members appear to have complementary and overlapping roles in regulating neural crest development, they have clear functional differences with regard to regulation of ERα expression. The global genomic binding pattern for TFAP2A and TFAP2C is highly similar. Genomic binding for TFAP2A and TFAP2C in the regulatory region for luminal-associated genes further demonstrated co-localization of the two factors. On the other hand, clear functional differences exist when comparing the effect on the pattern of gene expression following knockdown of TFAP2A vs. TFAP2C. In each case, knockdown of TFAP2C resulted in an abrogation of expression (RNA and protein) of the luminal-associated gene, whereas, knockdown of TFAP2A had minimal or no effect. By contrast, a known TFAP2A target gene, CDKN1A, was responsive to TFAP2A only.
2014-04-12 | GSE44257 | GEO
Project description:Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion in zebrafish, tfap2a mutants present abnormal alx3 expression patterns, Tfap2a binds alx loci, and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development by activating expression of ALX transcription factors.
2024-01-01 | GSE246685 | GEO
Project description:Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion in zebrafish, tfap2a mutants present abnormal alx3 expression patterns, Tfap2a binds alx loci, and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development by activating expression of ALX transcription factors.
2024-01-01 | GSE246806 | GEO
Project description:Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion in zebrafish, tfap2a mutants present abnormal alx3 expression patterns, Tfap2a binds alx loci, and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development by activating expression of ALX transcription factors.
2024-01-01 | GSE246805 | GEO