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Genomic Structure of the Promoters of the Human Estrogen Receptor-α Gene Demonstrate Changes in Chromatin Structure Induced by AP2γ
Journal article   Open access   Peer reviewed

Genomic Structure of the Promoters of the Human Estrogen Receptor-α Gene Demonstrate Changes in Chromatin Structure Induced by AP2γ

Eric R Schuur, Lisa A McPherson, George P Yang and Ronald J Weigel
The Journal of biological chemistry, Vol.276(18), pp.15519-15526
05/04/2001
DOI: 10.1074/jbc.M009001200
PMID: 11278455
url
https://doi.org/10.1074/jbc.M009001200View
Published (Version of record) Open Access

Abstract

Expression of human estrogen receptor-alpha (ERalpha) involves the activity from several promoters that give rise to alternate untranslated 5' exons. However, the genomic locations of the alternate 5' exons have not been reported previously. We have developed a contig map of the human ERalpha gene that includes all of the known alternate 5' exons. By using S1 nuclease and 5'- rapid amplification of cDNA ends, the cap sites for the alternate ERalpha transcripts E and H were identified. DNase I-hypersensitive sites specific to ERalpha-positive cells were associated with each of the cap sites. A DNase I-hypersensitive site, HS1, was localized to binding sites for AP2 in the untranslated region of exon 1 and was invariably present in the chromatin structure of ERalpha-positive cells. Overexpression of AP2gamma in human mammary epithelial cells generated the HS1-hypersensitive site. The ERalpha promoter was induced by AP2gamma in mammary epithelial cells, and trans-activation was dependent upon the region of the promoter containing the HS1 site. These results demonstrate that AP2gamma trans-activates the ERalpha gene in hormone-responsive tumors by inducing changes in the chromatin structure of the ERalpha promoter. These data are further evidence for a critical role for AP2 in the oncogenesis of hormone-responsive breast cancers.

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