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首页> 外文期刊>Molecular and Cellular Biology >Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.
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Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.

机译:宽间隔,直接重复的PuGGTCA元素充当不同类别核受体的混杂增强子。

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We describe here a novel class of cis-acting response elements for retinoid, vitamin D, and estrogen receptors which are widely spaced (10 to 200 bp) direct repeats (DRs) of the canonical 5'-AGGTCA half-site recognition motif (DR10 to DR200). In contrast to the specificity previously observed with shortly spaced DRs (DR1 to DR5), the different receptors bind promiscuously to these novel elements to activate transcription in the presence of retinoic acid (RA), vitamin D, or estrogen. The greatest RA-dependent transactivation, seen with DR15, was similar to that observed with the canonical DR5. Both RA receptors and retinoid X receptors contribute to transactivation through widely spaced DR elements. With the estrogen receptor, DR15 was one-third as efficient as the classical palindromic response element. A further increase of spacer lengths progressively decreased the efficiency of transactivation. No transactivation was seen with widely spaced DRs when the thyroid and retinoid X receptors were coexpressed in the presence of their ligands. The progesterone receptor was also unable to transactivate through a DR10 element composed of its cognate binding motifs. These results considerably extend the response element repertoire of nuclear receptors and suggest the existence of promiscuous transcriptional regulation through common response elements, as well as the possibility of receptor "cross-talk."
机译:我们在此描述类视黄醇,维生素D和雌激素受体的一类新型顺式作用响应元件,这些距离广泛分布于规范的5'-AGGTCA半位识别基序(DR10)的间隔较大(10至200 bp)的直接重复(DRs)到DR200)。与以前使用短距离DR(DR1至DR5)观察到的特异性相反,在视黄酸(RA),维生素D或雌激素存在的情况下,不同的受体混杂地结合到这些新元件上,从而激活转录。用DR15观察到的最大的RA依赖性反式激活与经典DR5观察到的相似。 RA受体和类维生素A X受体均通过相距较远的DR元素促进反式激活。有了雌激素受体,DR15的效率是经典回文响应元件的三分之一。间隔物长度的进一步增加逐渐降低了反式激活的效率。当甲状腺和维甲酸X受体在其配体存在下共表达时,在宽间隔的DR上未见到反式激活。孕激素受体也不能通过由其同源结合基序组成的DR10元件反式激活。这些结果大大扩展了核受体的反应元件库,并表明通过共同的反应元件存在混杂的转录调控,以及受体“串扰”的可能性。

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