Retinoid X receptor-alpha and apolipoprotein AI regulatory protein 1 differentially modulate 3,5,3'-triiodothyronine-induced transcription.
The formation of heterodimers with thyroid hormone receptor (TR) and other nuclear hormone receptors on thyroid hormone response elements (TREs) is important for T3-regulated gene transcription. The potential roles of retinoid X receptor-alpha (RXR alpha) and apolipoprotein regulatory protein-1 (ARP-1) in T3-mediated transcription were studied on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleotides (DR4), using electrophoretic mobility shift assays and transient transfection in CV-1 cells. It was shown that RXR alpha blocked liganded TR alpha-induced transcription. However, ARP-1 did not block T3/TR alpha-mediated transcription, although both TR alpha/RXR alpha and TR alpha/ARP-1 heterodimers had similar affinities for the TRE-DR4. In contrast, wild type ARP-1 reversed the blocking effect of RXR alpha on the liganded TR alpha-induced transcription, whereas a dimerization domain-deleted ARP-1 mutant (ARP-1 delta C) did not, suggesting that ARP-1 modulates T3-induced transcription through a dimerization process. Thus, the TRE-DR4 differentially responds to T3 at the transcriptional level by accommodating a battery of TR heterodimeric complexes.
Rhee
M
M
Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Ikeda
M
M
Chin
W W
WW
D000818:Animals; D001483:Base Sequence; D051836:COUP Transcription Factors; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism*
D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D004247:DNA