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An essential role of the Steroid receptor coactivator‐p300 pathway in thyroid hormone receptor mediated metamorphosis in Xenopus laevis
Author(s) -
Paul Bindu Diana,
Buchholz Daniel R,
Fu Liezhen,
Shi YunBo
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a966-c
Subject(s) - coactivator , xenopus , metamorphosis , biology , nuclear receptor , thyroid hormone receptor , endocrinology , medicine , nuclear receptor coactivator 3 , microbiology and biotechnology , receptor , thyroid , gene , transcription factor , genetics , botany , larva
Amphibian metamorphosis is among the most dramatic processes dependent on the thyroid hormone, T3. T3 binds thyroid hormone receptors (TRs), which repress or activate target genes by recruiting corepressors or coactivators, depending on the absence or presence of T3, respectively. Several cofactors for TR have been characterized in vitro . In comparison, fewer studies have addressed their developmental roles in vivo . We have studied the role of coactivators in postembryonic development using Xenopus laevis as a model system. A major advantage of the system is that tissues undergoing transitions are totally T3‐dependent despite undergoing diverse transformations and can be easily manipulated by blocking T3 synthesis or induced by adding T3 to the growth medium. Our studies show that the steroid receptor coactivator 3 (SRC3) is upregulated during metamorphosis and recruited to T3‐responsive promoters in a tissue‐and gene‐specific manner. Transgenic tadpoles overexpressing a dominant negative form of SRC3 or p300, a coactivator that interacts with SRCs, were impaired in natural and T3‐induced metamorphosis leading to arrested or delayed development or formation of tailed frogs. The dominant negative coactivators functioned by competing out endogenous coactivators and blocking expression of T3‐responsive genes. Taken together, our results provide the first in vivo role for the SRC‐p300 coactivator pathway during amphibian metamorphosis. Funding: NIH