THE THYROID-HORMONE RECEPTOR BINDS WITH OPPOSITE TRANSCRIPTIONAL EFFECTS TO A COMMON SEQUENCE MOTIF IN THYROID-HORMONE AND ESTROGEN RESPONSE ELEMENTS

THE THYROID-HORMONE RECEPTOR BINDS WITH OPPOSITE TRANSCRIPTIONAL EFFECTS TO A COMMON SEQUENCE MOTIF IN THYROID-HORMONE AND ESTROGEN RESPONSE ELEMENTS
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DOI:
10.1016/0092-8674(88)90194-8
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发表时间:
1988-07-29
期刊:
影响因子:
64.5
通讯作者:
ROSENFELD, MG
ROSENFELD, MG
中科院分区:
生物学1区
文献类型:
--
作者:
GLASS, CK;HOLLOWAY, JM;ROSENFELD, MG

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我们报道甲状腺激素(T3)受体与DNA识别序列结合,所述DNA识别序列是回文基序5“-TCAGGTCA. cntdot的变体。TGACCT-GA-3“,导致体内转录激活。该序列与卵黄蛋白原A2雌激素反应元件相同,除了在二分体对称中心缺少3 bp,我们称之为“缺口”。T3受体在体外以高亲和力结合雌激素应答元件,以及结合含有1-6 bp缺口的相同序列的变体。T3受体在体内不仅不能激活雌激素应答元件的转录,而且抑制雌激素依赖的反式激活。我们提出,T3受体结合雌激素反应元件在转录活性的形式和竞争雌激素受体结合,导致基因表达的净减少。这些数据表明,只有一个子集的T3受体DNA结合元件作为T3反应元件的功能。
We report that the thyroid hormone (T3) receptor binds to DNA recognition sequences that are variations of the palindromic motif 5''-TCAGGTCA .cntdot. TGACCT-GA-3'', resulting in transcriptional activation in vivo. This sequence is identical to the vitellogenin A2 estrogen response element except for the absence of 3 bp at the center of dyad symmetry, which we have termed a "gap". The T3 receptor binds to estrogen response elements with high affinity in vitro, as well as to variations of the same sequence containing gaps of 1-6 bp. The T3 receptor not only fails to activate transcription from estrogen response elements in vivo, but inhibits estrogen-dependent transactivation. We propose that the T3 receptor binds to estrogen response elements in a transcriptionally inactive form and competes for estrogen receptor binding, resulting in a net decrease in gene expression. These data reveal that only a subset of T3 receptor DNA-binding elements function as T3 response elements.