Differential DNA binding by monomeric, homodimeric, and potentially heteromeric forms of the thyroid hormone receptor.
Binding of the thyroid hormone receptor (TR) to thyroid hormone-responsive elements (TREs) is crucial for regulation of gene expression by thyroid hormone. The TR binds to each half-site of a palindromic TRE separately, as a monomer, or simultaneously, as a homodimer. In addition, the TR monomer interacts with a 42-kDa protein that may be responsible for an increase in the apparent size and stability of the TR-TRE complex after incubation with liver nuclear extract. The multiple DNA-binding forms of the TR contact the TRE differently but compete for binding in a dynamic equilibrium which is highly dependent on the relative concentrations of TR and nuclear protein. Thus, protein-protein interactions are likely to determine the context in which the TR binds to target genes and regulates the transcriptional response to thyroid hormone.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
M A
MA
Lazar
T J
TJ
Berrodin
H P
HP
Harding
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008110:Liver Extracts; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid
D008110:Liver Extracts; D046911:Macromolecular Substances; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D004247:DNA