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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 D 3 , Thyroid Hormone, and Retinoic Acid Receptors

1992; Taylor & Francis; Volume: 12; Issue: 9 Linguagem: Inglês

10.1128/mcb.12.9.4153-4163.1992

1098-5549

Austin J. Cooney, Sophia Y. Tsai, Bert W. O’Malley, Ming‐Jer Tsai,

Hypothalamic control of reproductive hormones

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.