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• W2004337331 startingPage "176" @default.
• W2004337331 abstract "Thyroid hormones (THs) play an important role in vertebrate development; however, the underlying mechanisms of their actions are still poorly understood. Zebrafish (Danio rerio) is an emerging vertebrate model system to study the roles of THs during development. In general, the response to THs relies on closely related proteins and mechanisms across vertebrate species, however some species-specific differences exist. In contrast to mammals, zebrafish has two TRalpha genes (thraa, thrab). Moreover, the zebrafish thraa gene expresses a TRalpha isoform (TRalphaA1) that differs from other TRs by containing additional C-terminal amino acids. C-terminal extensions, called F domains, are common in other members of the nuclear receptor superfamily and modulate the response of these receptors to hormones. Here we demonstrate that the F-domain constrains the transcriptional activity of zebrafish TRalpha by altering the selectivity of this receptor for certain coactivator binding motifs. We found that the F-domain of zebrafish TRalphaA1 is encoded on a separate exon whose inclusion is regulated by alternative splicing, indicating a regulatory role of the F-domain in vivo. Quantitative expression analyses revealed that TRalphaA1 is primarily expressed in reproductive organs whereas TRalphaB and the TRalphaA isoform that lacks the F-domain (TRalphaA1-2) appear to be ubiquitous. The relative expression levels of these TRalpha transcripts differ in a tissue-specific manner suggesting that zebrafish uses both alternative splicing and differential expression of TRalpha genes to diversify the cellular response to THs." @default.
• W2004337331 created "2016-06-24" @default.
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• W2004337331 creator A5085669031 @default.
• W2004337331 date "2008-01-01" @default.
• W2004337331 modified "2023-09-26" @default.
• W2004337331 title "An F-domain introduced by alternative splicing regulates activity of the zebrafish thyroid hormone receptor α" @default.
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• W2004337331 doi "https://doi.org/10.1016/j.ygcen.2007.04.012" @default.
• W2004337331 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3758257" @default.
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