Article

Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein

Department of Biochemistry, Saitama Medical School, Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/1994; 90(23):11117-21. DOI: 10.1073/pnas.90.23.11117
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ABSTRACT Estrogen receptor (ER)-binding fragments were isolated from human genomic DNA by using a recombinant ER protein. Using one of these fragments as a probe, we have identified an estrogen-responsive gene that encodes a putative zinc finger protein. It has a RING finger motif present in a family of apparent DNA-binding proteins and is designated estrogen-responsive finger protein (efp). efp cDNA contains a consensus estrogen-responsive element at the 3' untranslated region that can act as a downstream estrogen-dependent enhancer. Moreover, efp is regulated by estrogen as demonstrated at both the mRNA and the protein level in ER-positive cells derived from mammary gland. These data suggest that efp may represent an estrogen-responsive transcription factor that mediates phenotypic expression of the diverse estrogen action. Thus, the genomic binding-site cloning may be applicable for isolation of the target genes of other transcription factors.

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Available from: Akira Orimo, Aug 14, 2015
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    • "Identification of the target genes of transcription factors is critical to our understanding of transcriptional networks. For example, as canonical EREs were rarely found in promoter regions (O'Lone et al. 2004), it was difficult to identify the target genes of ERs by sequence motifs alone; filter binding (Inoue et al. 1993), computational approaches (Bourdeau et al. 2004; Kamalakaran et al. 2005) and ChIP on Chip (Carroll et al. 2005; Laganiere et al. 2005) have been applied to their identification . As these studies focused primarily on cultured cells, no information regarding whole organisms was available. "
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    • ".edu/ERTargetDB/SupplementaryInfo.pdf). For example, the reported ERE motifs GGTCATGGT- GACC in the human estrogen-responsive gene (efp) that encodes a RING finger protein (Inoue et al. 1993) and GGACACCATCTGTCC in the rat luteinizing hormone gene (Lhb) (Shupnik et al. 1989) were not found in the corresponding 7 kb promoter region. The 32 ER target genes that belong to the ER/X pathway of human, mouse and rat are reported to use the 'tethering,' mechanism with AP-1, Sp1 or NF-by individual laboratories (Supplementary Table 2 available at http://bioinformatics.med.ohio-state.edu/ERTargetDB/ "
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