Structure, tissue distribution and estrogen regulation of splice variants of the sea bream estrogen receptor α gene

Pinto, Patrícia I. S.; Teodósio, Rita; Socorro, Sílvia; Power, Deborah M.; Canário, Adelino V.M.

doi:10.1016/j.gene.2012.04.081

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…Consistent with studies in rodents and humans, alternatively spliced ERα variants have been identified in several fish species and some are orthologous to mammalian forms: for example, blue tilapia (Tan et al, 1996); rainbow trout (Pakdel et al, 2000); channel catfish (Xia et al, 1999; Patino et al, 2000); mangrove rivulus (Seo et al, 2006); killifish (Greytak and Callard, 2007); sea bream (Pinto et al, 2012); for additional references, see Table 3. In the rainbow trout, alternative use of multiple transcription and translation start sites results in both an N-truncated, short ERα isoform lacking the A domain and a full-length, long isoform, which differ significantly in their tissue distribution and transactivating properties (Menuet et al, 2001; Metivier et al, 2000; Pakdel et al, 2000; also see Discussion).…”

Section: Introductionsupporting

confidence: 55%

“…An exon 2b-3 deletion variant was amplified with ERα S specific primers (ERα S Δ2b-3), and is similar to two variants missing exon 2 (exon 3 in zebrafish) recently identified in sea bream (Pinto, 2012). The closest in frame start codon after the deletion is positioned at the beginning of exon 5, which predicts a protein lacking not only the A domain but also the first 214 amino acids of the AF-1 and DBD (B and C) domains, while retaining the full LBD/AF-2 region.…”

Section: Discussionmentioning

confidence: 99%

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

Cotter¹,

Yershov²,

Novillo³

et al. 2013

General and Comparative Endocrinology

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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.

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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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

Cotter¹,

Yershov²,

Novillo³

et al. 2013

General and Comparative Endocrinology

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“…Studies of fish gonads in aquaculture have shown the presence of the ER with a high affinity for E2. ER mRNA has been found in the male gonads of a variety of fish34567, including the Atlantic croaker Micropogonias undulatus 8, Tilapia spp 9,. Nile tilapia Oreochromis niloticus 10, channel catfish Ictalurus punctatus 11, zebrafish Danio rerio 12, Atlantic croaker Micropogonias undulatus 13, gilthead bream Sparus aurata 4 and rainbow trout Oncorhynchus mykiss 14.…”

mentioning

confidence: 99%

Molecular characterization and expression profile of the estrogen receptor α gene during different reproductive phases in Monopterus albus

Ding

Cao

et al. 2016

Sci Rep

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To understand the molecular mechanism of estrogen and to evaluate the role of the estrogen receptor in mediating estrogen action, the full-length cDNA of estrogen receptor α (ERα) was cloned from Monopterus albus, and its expression pattern and distribution were investigated. The ERα cDNA of M. albus includes an open reading frame of 1863 bp, a 140-bp 5’-untranslated region and a 797-bp 3’-untranslated region. Amino acid sequence homology analysis showed that the Monopterus albus ERα has a moderate degree of similarity with Sebastes schlegelii, Zoarces viviparus and Haplochromis burtoni (81.1%, 80.7% and 80.4%, respectively). Quantitative PCR results showed that the highest level of ERα expression was in the liver; the next highest level of expression was observed in the gonads, where it was expressed at high levels particularly in the ovary in developmental stages IV and V and in the testis in developmental stage II/III. Immunohistochemistry analysis showed that ERα was present as slender particles distributed mainly in the membranes of spermatocytes and oocytes in the testis and ovary, whereas no positive signal was observed in the cytoplasm of sperm cells. This report describes the first molecular characterization of full-length ERα and its tissue-specific distribution in M. albus.

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“…Several variants of both ERα and ERβ (Table 1) have been found in the testis of vertebrates [32][33][34][35][36][37][38] and, more recently, new exon-deleted ERα transcript variants have been isolated from piscine testis 39 . Many of these transcripts seem to modulate oestrogenic actions and may play a role in the regulation of spermatogenesis.…”

Section: Alternatively Spliced Variants Of Er and Ar In The Testismentioning

confidence: 99%

Structural variants of sex steroid hormone receptors in the testis: from molecular biology to physiological roles

Laurentino¹,

Pinto²,

Correia³

et al. 2012

OA Biotechnology

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IntroductionSex steroid hormones, androgens and oestrogens regulate diverse physiological processes by interacting with their intracellular protein receptors and modulating the expression of target genes. Classical sex steroid hormone receptors belong to the nuclear receptor superfamily, which forms the largest known family of transcription factors in eukaryotes. A common feature of sex steroid hormone receptors genes is the incidence of alternative splicing, a process that generates multiple variants from a single mRNA precursor molecule. This process facilitates the production of functionally distinct proteins and contributes to proteome diversity in higher eukaryotes. Herein we will critically review current information about the diversity of oestrogen receptors and androgen receptors variants, discussing their structural features and physiological functions. ConclusionThe identification of structural variants of both ERs and ARs in healthy testis and a broad range of vertebrate species, highlights the newly revealed complexity of SSHRs signalling mechanisms in this tissue.

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Structure, tissue distribution and estrogen regulation of splice variants of the sea bream estrogen receptor α gene

Cited by 14 publications

References 43 publications

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

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

Molecular characterization and expression profile of the estrogen receptor α gene during different reproductive phases in Monopterus albus

Structural variants of sex steroid hormone receptors in the testis: from molecular biology to physiological roles

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