Genomic Structure of the Promoters of the Human Estrogen Receptor-α Gene Demonstrate Changes in Chromatin Structure Induced by AP2Î
Expression of human estrogen receptor-α (ERα) involves the activity from several promoters that give rise to alternate untranslated 5Ⲡexons. However, the genomic locations of the alternate 5Ⲡexons have not been reported previously. We have developed a contig map of the human ERα gene that i...
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Published in | The Journal of biological chemistry Vol. 276; no. 18; p. 15519 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
04.05.2001
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Online Access | Get full text |
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Summary: | Expression of human estrogen receptor-α (ERα) involves the activity from several promoters that give rise to alternate untranslated
5â² exons. However, the genomic locations of the alternate 5â² exons have not been reported previously. We have developed a
contig map of the human ERα gene that includes all of the known alternate 5â² exons. By using S1 nuclease and 5â²- rapid amplification
of cDNA ends, the cap sites for the alternate ERα transcripts E and H were identified. DNase I-hypersensitive sites specific
to ERα-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 ERα-positive cells.
Overexpression of AP2γ in human mammary epithelial cells generated the HS1-hypersensitive site. The ERα promoter was induced
by AP2γ in mammary epithelial cells, and trans-activation was dependent upon the region of the promoter containing the HS1
site. These results demonstrate that AP2γ trans-activates the ERα gene in hormone-responsive tumors by inducing changes in
the chromatin structure of the ERα promoter. These data are further evidence for a critical role for AP2 in the oncogenesis
of hormone-responsive breast cancers. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M009001200 |