The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors
The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors
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DOI：
10.1073/pnas.95.10.5474
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发表时间：
1998-05-12
影响因子：
11.1
通讯作者：
Bradfield, CA
中科院分区：
文献类型：
--
作者：
Hogenesch, JB;Gu, YZ;Bradfield, CA
我们报告说，MOP 3是一个通用的二聚伙伴的一个子集的基本螺旋-环-螺旋（bHLH）-PER-ARNT-SIM（PAS）超家族的转录调节因子。我们证明MOP 3与MOP 4、CLOCK、缺氧诱导因子1 α（HIF 1 α）和HIF 2 α相互作用。DNA选择方案揭示MOP 3 MOP 4异二聚体结合含CACGTGA的DNA元件。瞬时转染实验证明MOP 3-MOP 4和MOP 3-CLOCK复合物在COS-1细胞中结合该元件并驱动从连接的荧光素酶报告基因的转录，我们还推导了MOP 3-HIF 1 α复合物的高亲和力DNA结合位点（TACGTGA）并使用瞬时转染实验证明MOP 3-HIF 1 α和MOP 3-HIF 2 α异二聚体结合该元件，驱动转录，并响应细胞缺氧。终于来了我们发现MOP 3 mRNA表达在许多组织中与其体内四种潜在的配偶体分子中的每一种重叠。
We report that MOP3 is a general dimerization partner for a subset of the basic-helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) superfamily of transcriptional regulators. We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia inducible factor 1 alpha (HIF1 alpha), and HIF2 alpha. A DNA selection protocol revealed that the MOP3 MOP4 heterodimer bound a CACGTGA-containing DNA element, Transient transfection experiments demonstrated that the MOP3-MOP4 and MOP3-CLOCK complexes bound this element in COS-1 cells and drove transcription from a linked luciferase reporter gene, We also deduced the high-affinity DNA binding sites for MOP3-HIF1 alpha complex (TACGTGA) and used transient transfection experiments to demonstrate that the MOP3-HIF1 alpha and MOP3-HIF2 alpha heterodimers bound this element, drove transcription, and responded to cellular hypoxia. Finally. we found that MOP3 mRNA expression overlaps in a number of tissues with each of its four potential partner molecules in vivo.