PUBLICATION
An F-domain introduced by alternative splicing regulates activity of the zebrafish thyroid hormone receptor alpha
- Authors
- Takayama, S., Hostick, U., Haendel, M., Eisen, J., and Darimont, B.
- ID
- ZDB-PUB-070629-26
- Date
- 2008
- Source
- General and comparative endocrinology 155(1): 176-189 (Journal)
- Registered Authors
- Eisen, Judith S., Haendel, Melissa A.
- Keywords
- Thyroid hormone, Thyroid hormone receptor (TR), Isoforms, F-domain; Zebrafish (Danio rerio), Alternative splicing, Tissue-specific expression, Coactivator interaction
- MeSH Terms
-
- Alternative Splicing/physiology*
- Amino Acid Sequence
- Animals
- Base Sequence
- Cells, Cultured
- Chlorocebus aethiops
- DNA Mutational Analysis
- Embryo, Nonmammalian
- Gene Deletion
- Gene Expression Regulation, Developmental
- Models, Biological
- Models, Molecular
- Molecular Sequence Data
- Protein Structure, Tertiary/genetics
- Protein Structure, Tertiary/physiology
- Sequence Homology, Amino Acid
- Thyroid Hormone Receptors alpha/chemistry
- Thyroid Hormone Receptors alpha/genetics*
- Thyroid Hormone Receptors alpha/metabolism*
- Thyroid Hormone Receptors alpha/physiology*
- Transcriptional Activation
- Zebrafish/genetics*
- PubMed
- 17583703 Full text @ Gen. Comp. Endocrinol.
Citation
Takayama, S., Hostick, U., Haendel, M., Eisen, J., and Darimont, B. (2008) An F-domain introduced by alternative splicing regulates activity of the zebrafish thyroid hormone receptor alpha. General and comparative endocrinology. 155(1):176-189.
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
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping