Mechanisms for synergistic activation of thyroid hormone receptor and retinoid X receptor on different response elements.
The thyroid hormone receptors (TR) form heterodimers with the retinoid X receptors (RXR) and activate target genes through thyroid-responsive elements (TRE). Heterodimerization elevates the DNA binding efficiency and thus can result in functional synergism between TR and RXR. Here we demonstrate that DNA sequences dictate the cooperative activation between TR and RXR despite the high affinity binding of the heterodimer to those TREs. We provide evidence that the C-terminal activation domain of RXR can modulate the triiodothyronine (T3) responsiveness of TR/RXR heterodimers on reporter genes without altering the DNA binding properties of the heterodimers. The modulation function of this relatively small region is under the control of specific TRE sequences and promoter context. These data indicate that this C-terminal region of RXR is likely involved in receptor-cellular factor(s) interactions. Finally, we propose that the synergistic activation by TR and RXR is achieved through elevated DNA binding and, dependent on the DNA sequence, the interaction of RXR with other transcription factors.
Leng
X
X
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Blanco
J
J
Tsai
S Y
SY
Ozato
K
K
O'Malley
B W
BW
Tsai
M J
MJ
D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D004357:Drug Synergism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors