Journal
BMC GENOMICS
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1471-2164-9-476
Keywords
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Funding
- National High Technology Research and Development [2006AA02A305]
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Background: Estrogen receptor alpha (ER alpha) is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ER alpha, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE) with a reporter gene. This allowed the cellular activity of ER alpha, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results: From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131) as a repressor of ER alpha mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ER alpha in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERa interrupts or prevents ER alpha binding to the estrogen response element (ERE). In addition, ZNF131 was able to suppress the expression of pS2, an ER alpha target gene. Conclusion: We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ER alpha-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ER alpha regulation in mammalian cells.
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