Pereira F A, Qiu Y, Tsai M J, Tsai S Y
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):503-8. doi: 10.1016/0960-0760(95)00097-j.
Members of the steroid/thyroid hormone receptor superfamily such as TR, RAR, RXR and VDR are known to play important roles in regulation of gene expression during development, differentiation and homeostasis. COUP-TFs are orphan members of this superfamily of nuclear receptors and have been shown to negatively regulate the ability of these nuclear receptors to transactivate target genes. Two different mechanisms are implicated in this repression. First, COUP-TFs bind to AGGTCA direct repeats and palindromes with various spacings, which include response elements for TR, RAR, RXR and VDR, allowing for direct competition of COUP-TFs for the response elements. Second, COUP-TFs can heterodimerize with RXRs, the essential cofactor for effective binding of VDR, TRs and RARs to their cognate response elements. The physiological significance of this negative effect of COUP-TF on the activity of these receptors has been analyzed. Detection of COUP-TF transcripts during mouse development reveal discrete spatial and temporal expression domains consistent with COUP-TFs being involved in regulation of gene expression during embryogenesis. Transcripts are localized within discrete regions of the central and peripheral nervous system including the inner ear. In addition, COUP-TFs are found in many tissues including testes, ovary, prostate, skin, kidney, lung, stomach, intestine, pancreas and salivary gland. Some of these expression domains colocalize with those of TR, RAR, and RXR. The simultaneous expression of these genes raise the possibility that COUP-TFs can act as negative regulatory factors during development and differentiation.
类固醇/甲状腺激素受体超家族的成员，如甲状腺激素受体（TR）、视黄酸受体（RAR）、维甲酸X受体（RXR）和维生素D受体（VDR），在发育、分化和体内平衡过程中对基因表达的调控起着重要作用。鸡卵清蛋白上游启动子转录因子（COUP-TFs）是这个核受体超家族的孤儿成员，已被证明能负向调节这些核受体激活靶基因的能力。这种抑制作用涉及两种不同的机制。首先，COUP-TFs能与具有不同间隔的AGGTCA直接重复序列和回文序列结合，其中包括TR、RAR、RXR和VDR的反应元件，从而使COUP-TFs与反应元件直接竞争。其次，COUP-TFs能与RXR形成异源二聚体，而RXR是VDR、TR和RAR有效结合其同源反应元件所必需的辅因子。已分析了COUP-TF对这些受体活性的这种负面影响的生理意义。在小鼠发育过程中检测COUP-TF转录本，发现其离散的空间和时间表达域，这与COUP-TFs参与胚胎发生过程中的基因表达调控一致。转录本定位于中枢和外周神经系统的离散区域，包括内耳。此外，在许多组织中都发现了COUP-TFs，包括睾丸、卵巢、前列腺、皮肤、肾脏、肺、胃、肠、胰腺和唾液腺。其中一些表达域与TR、RAR和RXR的表达域共定位。这些基因的同时表达增加了COUP-TFs在发育和分化过程中可作为负调节因子的可能性。
