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J. Biol. Chem., Vol. 269, Issue 40, 24699-24705, 10, 1994
M Ranjan, J Wong and YB Shi
We report here the detailed analysis of the promoter of a thyroid hormone
receptor (TR) gene that is regulated by the hormone itself. The receptor
gene, TR beta A, is one of the two TR beta genes in Xenopus laevis. It has
two transcription start sites. The mRNAs derived from one of them are
up-regulated by thyroid hormone, whereas those derived from the other are
independent of the hormone. We have characterized the hormone-inducible
promoter using a transient transfection assay in a Xenopus tissue culture
cell line (A6). Deletion and mutational analysis identifies the first
amphibian thyroid hormone response element (TRE). This TRE consists of near
perfect direct repeats of AGGTCA with a 4-base pair spacing similar to
mammalian TREs. The TRE forms specific complexes with extracts of A6 cells
that have similar sequence specificities as those found for the complexes
between mammalian TRs and TREs. However, unlike TREs found in other thyroid
hormone-inducible promoters, this TRE is located at the putative
transcription start site and mediates transcriptional repression by
unliganded TRs. The addition of thyroid hormone at physiological
concentrations overcomes the repression and induces further transcriptional
activation at higher concentrations. These results suggest a potential
mechanism for the regulation of amphibian metamorphosis, a process that is
entirely controlled by thyroid hormone.
Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site
Laboratory of Molecular Embryology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892.
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