Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.
Alignment of natural chicken ovalbumin upstream promoter transcription factor (COUP-TF) response elements shows that, in addition to the predominant direct repeat of the GGTCA motif with a 2-bp spacing, there are other functional COUP elements with variations in the GGTCA orientation and spacing. We systematically analyzed the binding of in vitro-synthesized COUP-TFs and showed that COUP-TF is capable of binding to oligonucleotides containing both direct repeats and palindromes and with different spacings of the GGTCA repeats. Subsequently, we analyzed four possible mechanisms proposed to explain how COUP-TF could bind to these spatial variations of the GGTCA repeat. We demonstrated that the functional DNA-binding form of COUP-TF is a dimer which requires two GGTCA half-sites to bind DNA. We demonstrated that the COUP-TF dimer undergoes a remarkable structural adaptation to accommodate binding to these spatial variants of the GGTCA repeats. A functional consequence of the promiscuous DNA binding of COUP-TF is its ability to down-regulate hormonal induction of target gene expression by other members of the steroid-thyroid hormone receptor superfamily such as the vitamin D3, thyroid hormone, and retinoic acid receptors. Our data indicate that COUP-TF may have an important role in hormonal regulation of gene expression by these receptors.
Cooney
A J
AJ
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Tsai
S Y
SY
O'Malley
B W
BW
Tsai
M J
MJ
D000818:Animals; D001483:Base Sequence; D051838:COUP Transcription Factor I; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002762:Cholecalciferol / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology*; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid; D012091:Repetitive Sequences, Nucleic Acid; D012996:Solutions; D013963:Thyroid Hormones / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014212:Tretinoin
D051838:COUP Transcription Factor I; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D012996:Solutions; D013963:Thyroid Hormones; D014157:Transcription Factors; D002762:Cholecalciferol; D014212:Tretinoin; D004247:DNA