The zinc finger/homeodomain protein δEF1 mediates estrogen-specific induction of the ovalbumin gene
The zinc finger/homeodomain protein δEF1 mediates estrogen-specific induction of the ovalbumin gene
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DOI：
10.1016/s0303-7207(02)00088-6
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发表时间：
2002-06-28
影响因子：
4.1
通讯作者：
Sanders, MM
中科院分区：
文献类型：
--
作者：
Dillner, NB;Sanders, MM
卵清蛋白 (Ov) 基因的调节受到精确的发育、组织特异性和激素线索的严格控制。 Ov 基因由四类类固醇激素转录激活：雌激素、雄激素、糖皮质激素和孕激素。尽管过去 30 年来它一直作为研究多激素基因调控的模型，但将每种激素信号传递给 Ov 基因的途径在很大程度上尚不清楚。广泛的接头扫描仪和点突变分析揭示了雌激素、雄激素、黄体酮或糖皮质激素诱导其所必需的元素，但未能识别任何一种类固醇激素作用所特有的任何元素。这些观察结果与 Ov 基因间接受类固醇激素调节的观察结果相结合，表明这些信号可能都诱导相同的转录因子。然而，我们在这里鉴定了 Ov 基因 5' 侧翼区域的两个顺式作用 DNA 元件，它们是雌激素诱导所需的，但不是雄激素或孕激素诱导所需的。这些元件相对于转录起始点跨越-152至-146和-8、10至-806。这意味着雌激素通过与雄激素或孕激素不同的途径诱导 Ov 基因。凝胶迁移率变化分析表明，雌激素特异性序列与雌激素诱导转录因子 deltaEF1 结合，表明 deltaEF1 在介导 Ov 基因的雌激素信号中发挥着独特的作用。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Regulation of the ovalbumin (Ov) gene is strictly controlled by precise developmental, tissue-specific, and hormonal cues. The Ov gene is transcriptionally activated by four classes of steroid hormones: estrogens, androgens, glucocorticoids, and progestins. Although it has served as a model to study multi-hormone gene regulation for the past 30 years, the pathways that relay each hormone signal to the Ov gene are largely unclear. Extensive linker-scanner and point mutation analysis has revealed elements necessary for its induction by estrogen, androgen, progesterone, or glucocorticoid but has failed to identify any elements that are specific to the action of any one steroid hormone. These observations in conjunction with the observation that the Ov gene is indirectly regulated by steroid hormones suggest that these signals may all induce the same transcription factor. However, here we have identified two cis-acting DNA elements in the 5' flanking region of the Ov gene that are required for induction by estrogen, but not by androgen or progesterone. These elements span -152 to -146 and -8 10 to -806 with respect to the start point of transcription. This implies that estrogen induces the Ov gene by a separate pathway than do androgens or progestins. Gel mobility shift assays demonstrate that the estrogen-specific sequences bind the estrogen inducible transcription factor deltaEF1, suggesting that deltaEF1 plays a distinct role in mediating the estrogen signal to the Ov gene. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.