Dataset Information

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.

ABSTRACT: BACKGROUND: Activator protein 2 gamma (AP-2gamma) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2gamma has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. METHODS: To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2gamma binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. RESULTS: 20 novel DNA fragments proximal to potential AP-2gamma targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2gamma target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2gamma. Decreased expression and overexpression of AP-2gamma in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2gamma directly regulates them. CONCLUSION: This suggested that AP-2gamma can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.

SUBMITTER: Ailan H

PROVIDER: S-EPMC3224728 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.

Ailan He H Xiangwen Xiao X Daolong Ren R Lu Gan G Xiaofeng Ding D Xi Qiao Q Xingwang Hu H Rushi Liu L Jian Zhang Z Shuanglin Xiang X

BMC cancer 20090811

<h4>Background</h4>Activator protein 2 gamma (AP-2gamma) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2gamma has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.<h4>Methods</h4>To identify the gene targets that mediate its effects, we performed chromatin immunoprecipita ...[more]

PMID: 19671168

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Project description:BackgroundIn the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool for examining gene regulation. Crosslinked chromatin is immunoprecipitated with antibodies against specific transcription factors, thus enriching for sequences bound in vivo by these factors in the immunoprecipitated DNA. Cloning and sequencing the immunoprecipitated sequences allows identification of transcription factor target genes. Routinely, thousands of such sequenced clones are used in BLAST searches to map their exact location in the genome and the genes located in the vicinity. These genes represent potential targets of the transcription factor of interest. Such bioinformatics analysis is very laborious if performed manually and for this reason there is a need for developing bioinformatic tools to automate and facilitate it.ResultsIn order to facilitate this analysis we generated TF Target Mapper (Transcription Factor Target Mapper). TF Target Mapper is a BLAST search tool allowing rapid extraction of annotated information on genes around each hit. It combines sequence cleaning/filtering, pattern searching and BLAST searches with extraction of information on genes located around each BLAST hit and comparisons of the output list of genes or gene ontology IDs with user-implemented lists. We successfully applied and tested TF Target Mapper to analyse sequences bound in vivo by the transcription factor GATA-1. We show that TF Target Mapper efficiently extracted information on genes around ChIPed sequences, thus identifying known (e.g. alpha-globin and zeta-globin) and potentially novel GATA-1 gene targets.ConclusionTF Target Mapper is a very efficient BLAST search tool that allows the rapid extraction of annotated information on the genes around each hit. It can contribute to the comprehensive bioinformatic transcriptome/regulome analysis, by providing insight into the mechanisms of action of specific transcription factors, thus helping to elucidate the pathways these factors regulate.

Dataset Information

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.

Publications

Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.

Similar Datasets

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