Triiodothyronine (T3) decreases binding to DNA by T3-receptor homodimers but not receptor-auxiliary protein heterodimers.
Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand.
Yen
P M
PM
Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02115.
Darling
D S
DS
Carter
R L
RL
Forgione
M
M
Umeda
P K
PK
Chin
W W
WW
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004586:Electrophoresis; D005786:Gene Expression Regulation; D006801:Humans; D009113:Muramidase / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D004247:DNA; D009113:Muramidase; D009218:Myosins