PMID: 2119495Sep 11, 1990Paper

Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor

Nucleic Acids Research
A Weisz, R Rosales

Abstract

Transcription of the proto-oncogene c-fos is stimulated by 17 beta-estradiol in estrogen responsive human and rat cells. To understand the molecular mechanisms of estrogen regulation of c-fos gene transcription, the human c-fos gene promoter, with 2.25 Kb of 5'-flanking DNA, was cloned upstream of the bacterial CAT gene and tested for estrogen regulation by transient transfection in HeLa cells. When an expression vector coding for the human estrogen receptor was co-transfected with the fos -CAT reporter, the promoter was found to respond to 17 beta-estradiol. An element responsible for estrogen induction was mapped in a 240 bp region localized 1060 to 1300 bases upstream of the startsite of transcription of the gene. Sequence analysis revealed, clustered in a 19 bp sub-region, a sequence corresponding to an imperfectly palindromic ERE: CGGCAGCGTGACC and two sequences: CTGAG and GTGAC, homologous to the core sequence of AP-1 transcription factor binding sites. A synthetic oligonucleotide reproducing this sub-region binds 'in vitro' both the estrogen receptor and AP-1 factor(s) and confers estrogen-responsivity to the HSV-tk gene promoter. Transcriptional activation by the estrogen receptor is prevented by mutations in the fos ER...Continue Reading

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