HALF-SITE SPACING AND ORIENTATION DETERMINES WHETHER THYROID-HORMONE AND RETINOIC ACID RECEPTORS AND RELATED FACTORS BIND TO DNA RESPONSE ELEMENTS AS MONOMERS, HOMODIMERS, OR HETERODIMERS
HALF-SITE SPACING AND ORIENTATION DETERMINES WHETHER THYROID-HORMONE AND RETINOIC ACID RECEPTORS AND RELATED FACTORS BIND TO DNA RESPONSE ELEMENTS AS MONOMERS, HOMODIMERS, OR HETERODIMERS
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DOI：
10.1210/me.6.3.429
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发表时间：
1992-03-01
影响因子：
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通讯作者：
SAMUELS, HH
中科院分区：
文献类型：
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作者：
FORMAN, BM;CASANOVA, J;SAMUELS, HH
甲状腺激素受体（T3R）和视黄酸受体（RAR）是核受体亚家族的成员，能够识别相似的DNA序列。T3R和RAR的天然反应元件由两个或多个假定的半位点结合基序组成，由不同大小的核苷酸间隙分隔成不完美的直接或反向重复序列。为了阐明T3R、RAR和相关因子如何识别DNA应答元件，我们分析了纯化受体与一系列由不同大小核苷酸间隙分隔的理想AGGTCA半位点的反向和直接重复的相互作用。我们的研究结果表明，RAR和T3R可以作为单体结合到半位点上，并且根据半位点之间的取向和距离，也可以作为同型二聚体或T3R-RAR异源二聚体结合。T3R还与真核细胞中的一个或多个核因子结合，作为异源二聚体与某些DNA元件结合。因此，半位点的方向和间距在决定受体和核因子的结构与特定DNA元件相互作用方面起着核心作用。这与这些因子参与可逆蛋白-蛋白相互作用的能力一起，有助于扩大和多样化由T3R、RAR和该核受体亚家族相关成员介导的反应。
The receptors for thyroid hormone (T3R) and retinoic acid (RAR) are members of a nuclear receptor subfamily that are capable of recognizing similar DNA sequences. Native response elements for T3R and RAR consist of two or more putative half-site binding motifs organized as imperfect direct or inverted repeats separated by different sized nucleotide gaps. To clarify how T3R, RAR, and related factors recognize DNA response elements, we analyzed the interaction of purified receptors with a series of inverted and direct repeats of an idealized AGGTCA half-site separated by different sized nucleotide gaps. Our results indicate that RAR and T3R can bind to half-sites as monomers and, depending on the orientation and distance between half-sites, also bind as homodimers or T3R-RAR heterodimers. T3R also binds to certain DNA elements as a heterodimer with one or more nuclear factors from eucaryotic cells. Thus, the orientation and spacing of half-sites play a central role in determining which configuration of receptors and nuclear factors will interact with a specific DNA element. This along with the ability of these factors to participate in reversible protein-protein interactions serve to broaden and diversify the responses mediated by T3R, RAR, and related members of this nuclear receptor subfamily.