A Role for Basic Transcription Element-binding Protein 1 (BTEB1) in the Autoinduction of Thyroid Hormone Receptor

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 02/2008; 283(4):2275-85. DOI: 10.1074/jbc.M709306200
Source: PubMed


Thyroid hormone (T3) induces gene regulation programs necessary for tadpole metamorphosis. Among the earliest responses to T3 are the up-regulation of T3 receptor β (TRβ; autoinduction) and BTEB1 (basic transcription element-binding protein 1). BTEB1 is a member of the Krüppel
family of transcription factors that bind to GC-rich regions in gene promoters. The proximal promoter of the Xenopus laevis TrβA gene has seven GC-rich sequences, which led us to hypothesize that BTEB1 binds to and regulates TrβA. In tadpoles and the frog fibroblast-derived cell line XTC-2, T3 up-regulated Bteb1 mRNA with faster kinetics than TrβA, and Bteb1 mRNA correlated with increased BTEB1 protein expression. BTEB1 bound to GC-rich sequences in the proximal TrβA promoter in vitro. By using chromatin immunoprecipitation assay, we show that BTEB1 associates with the TrβA promoter in vivo in a T3 and developmental stage-dependent manner. Induced expression of BTEB1 in XTC-2 cells caused accelerated and enhanced autoinduction
of the TrβA gene. This enhancement was lost in N-terminal truncated mutants of BTEB1. However, point mutations in the zinc fingers of
BTEB1 that destroyed DNA binding did not alter the activity of the protein on TrβA autoinduction, suggesting that BTEB1 can function in this regard through protein-protein interactions. Our findings support
the hypothesis that BTEB1 associates with the TrβA promoter in vivo and enhances autoinduction, but this action does not depend on its DNA binding activity. Cooperation among the protein products
of immediate early genes may be a common mechanism for driving developmental signaling pathways.

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    • "A number of studies have shown that the T3-dependent recruitment of various cofactor complexes correlates with local histone modifications, particularly acetylation and methylations, and gene regulation at target genes during metamorphosis 36-39, 47, 49-56. In addition to histone modifications, gene activation by liganded TR in the frog oocyte transcription system, where the DNA is chromatinized, also leads to chromatin disruption 57-59, resulting in a loss of up to 3 nucleosomes per receptor binding locus 58. "
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    • "This helps to ensure proper premetamorphic growth and prevent premature metamorphosis [16,26]. When T3 becomes available, liganded TR recruits histone modifying coactivator complexes to these target genes, leading to histone modifications, chromatin remodeling and gene activation [18,19,22,27-31]. This results in metamorphic transformations of different organs. "
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    • "In premetamorphic Xenopus laevis tadpoles, TR recruits corepressor complexes to target genes when T3 is absent and this recruitment is important to keep the T3-inducible genes repressed, thus regulating metamorphic timing (Figure 1) [31,36-38]. After stage 55, when endogenous T3 becomes available, corepressor complexes are released and coactivator complexes are recruited by TR, this leads to the activation of T3 target genes and metamorphosis [33,34,39-43]. "
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