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Multiple structurally distinct ERa mRNA variants in zebrafish are differentially expressed by tissue type, stage of development and estrogen exposure

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dc.contributor.author Cotter, Kellie A. spa
dc.contributor.author Yershov, A. spa
dc.contributor.author Novillo Villajos, Apolonia spa
dc.contributor.author Callard, Gloria V. spa
dc.date.accessioned 2014-03-18T10:09:17Z
dc.date.available 2014-03-18T10:09:17Z
dc.date.issued 2013 spa
dc.identifier.citation Cotter, K. A., Yershov, A., Novillo-Villajos, A., & Callard, G. V. (2013). Multiple structurally distinct ERa mRNA variants in zebrafish are differentially expressed by tissue type, stage of development and estrogen exposure. General and Comparative Endocrinology, 194, 217-229. spa
dc.identifier.uri http://hdl.handle.net/11268/2159
dc.description.abstract It is well established that estrogen-like environmental chemicals interact with the ligand-binding site of estrogen receptors (ER) to disrupt transcriptional control of estrogen responsive targets. Here we investigate the possibility that estrogens also impact splicing decisions on estrogen responsive genes, such as that encoding ERα itself. Targeted PCR cloning was applied to identify six ERα mRNA variants in zebrafish. Sequencing revealed alternate use of transcription and translation start sites, multiple exon deletions, intron retention and alternate polyadenylation. As determined by quantitative (q)PCR, N-terminal mRNA variants predicting long (ERαL) and short (ERαS) isoforms were differentially expressed by tissue-type, sex, stage of development and estrogen exposure. Whereas ERαL mRNA was diffusely distributed in liver, brain, heart, eye, and gonads, ERαS mRNA was preferentially expressed in liver (female > male) and ovary. Neither ERαL nor ERαS transcripts varied significantly during development, but 17β-estradiol selectively increased accumulation of ERαS mRNA (~170-fold by 120 hpf), an effect mimicked by bisphenol-A and diethylstilbestrol. Significantly, a C-truncated variant (ERαS-Cx) lacking most of the ligand binding and AF-2 domains was transcribed exclusively from the short isoform promoter and was similar to ERαS in its tissue-, stage- and estrogen inducible expression. These results support the idea that promoter choice and alternative splicing of the esr1 gene of zebrafish are part of the autoregulatory mechanism by which estrogen modulates subsequent ERα expression, and further suggest that environmental estrogens could exert some of their toxic effects by altering the relative abundance of structurally and functionally distinct ERα isoforms. spa
dc.language.iso eng spa
dc.title Multiple structurally distinct ERa mRNA variants in zebrafish are differentially expressed by tissue type, stage of development and estrogen exposure spa
dc.type article spa
dc.description.impact 2.674 JCR (2013) Q3, 64/123 Endocrinology & metabolism spa
dc.identifier.doi 10.1016/j.ygcen.2013.09.014 spa
dc.rights.accessRights closedAccess en
dc.subject.unesco Endocrinología spa
dc.subject.unesco Genética humana spa
dc.peerreviewed Si spa


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