Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Genomic structure of the promoters of the human estrogen receptor-alpha gene demonstrate changes in chromatin structure induced by AP2gamma. 1127 55

The human estrogen receptor-alpha (hER alpha) gene is a complex genomic unit exhibiting alternative splicing and promoter usage in a tissue-specific manner. During the investigation of new hER alpha mRNA variants by rapid amplification of 5' cDNA ends, we identified a cDNA in which the acceptor site of exon 1A, into which the different leader exons are normally alternatively spliced, was spliced accurately the 3' extremity of exon 1A (scrambled 1A-->1A hER alpha cDNA). Reverse transcription-PCR and S1 nuclease mapping analysis revealed that 1A-->1A hER alpha transcripts were not circular RNAs constituted by exon 1A only but corresponded to linear polyadenylated hER alpha RNAs composed of the eight coding exons of the hER alpha gene and characterized by a duplication of exon 1A. Genomic Southern blot experiments excluded the hypothesis of duplication of hER alpha exon 1A in the human genome. Therefore, these data suggested that 1A-->1A hER alpha transcripts were likely generated by trans-splicing. The production of such transcripts by trans-splicing of pre-mRNAs generated from a chimeric gene formed by a single hER alpha exon 1A, exon 2, and their flanking intronic regions was demonstrated in transient transfection experiments. Therefore, in addition to the alternative cis-splicing, the hER alpha gene is also subject to natural trans-splicing.
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PMID:Natural trans-spliced mRNAs are generated from the human estrogen receptor-alpha (hER alpha) gene. 1201 Oct 94


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