Basal and thyroid hormone receptor auxiliary protein-enhanced binding of thyroid hormone receptor isoforms to native thyroid hormone response elements.
There are three known isoforms of the rat thyroid hormone receptor, TR alpha-1, TR beta-1, and TR beta-2. The first two are expressed in all tissues, whereas TR beta-2 appears to be expressed only in the pituitary. The differences in the roles of the three receptor isoforms are unknown, but may involve preferential interaction with different subsets of thyroid hormone-regulated genes in different tissues. We tested the binding of the three TR isoforms to putative thyroid hormone response elements (TREs) from genes that are expressed in the pituitary or other tissues and are regulated by thyroid hormone. In vitro translated 35S-labeled rat TR alpha-1, rat TR beta-2, and human TR beta-1 receptors were bound to a battery of biotinylated synthetic deoxyribonucleotides containing naturally occurring putative TREs from genes expressed either in only pituitary (rat glycoprotein hormone alpha-subunit, TSH beta-subunit, and GH) or in nonpituitary (rat alpha-myosin heavy chain, malic enzyme, and Moloney murine leukemia virus promoter) tissues. All three receptor forms bound to each of the TREs. TR beta-2 did not show preferential binding to TREs of pituitary-specific genes compared to TR beta-1. Additionally, TR alpha-1 had a similar TRE-binding pattern as the TR beta s, except for possibly less binding to rat glycoprotein hormone alpha-subunit TRE. Finally, rat pituitary and liver nuclear extracts enhanced TR binding to TREs, with the greatest enhancement seen with the alpha-subunit TRE. These studies suggest that all TR isoforms bind similarly to native TREs. Also, TR binding to TREs can be differentially enhanced by interactions with nuclear proteins.
Yen
P M
PM
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Darling
D S
DS
Chin
W W
WW
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000494:pharmacology; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D013963:Thyroid Hormones / Q000494:pharmacology*
D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D004247:DNA