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首页> 外文期刊>Journal of Molecular Biology >A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1)
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A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1)

机译:孤儿核受体,生殖细胞核因子(GCNF)和肝受体同源物 - 1(LRH-1)对OCT4调节的结构调查

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摘要

Oct4 is a transcription factor required for maintaining pluripotency and self-renewal in stem cells. Prior to differentiation, Oct4 must be silenced to allow for the development of the three germ layers in the developing embryo. This fine-tuning is controlled by the nuclear receptors (NRs), liver receptor homolog-1 (LRH-1) and germ cell nuclear factor (GCNF). Liver receptor homolog-1 is responsible for driving the expression of Oct4 where GCNF represses its expression upon differentiation. Both receptors bind to a DRO motif located within the Oct4 promoter. Here, we present the first structure of mouse GCNF DNA-binding domain in complex with the Oct4 DRO. The overall structure revealed two molecules bound in a head-to-tail fashion on opposite sides of the DNA. Additionally, we solved the structure of the human LRH-1 DNA-binding domain bound to the same element. We explore the structural elements that govern Oct4 recognition by these two NRs. (C) 2016 Elsevier Ltd. All rights reserved.
机译:OCT4是维持干细胞中维持多能性和自我更新所需的转录因子。 在分化之前,OCT4必须沉默以允许在发育中胚胎中的三种胚层的发展。 这种微调由核受体(NRS),肝受体同源物 - 1(LRH-1)和生殖细胞核因子(GCNF)控制。 肝受体同源物-1负责驱动OCT4的表达,其中GCNF在分化时抑制其表达。 两个受体都与位于Oct4启动子内的DRO基序结合。 在这里,我们介绍了与Oct4 DRO复合物中的小鼠GCNF DNA结合结构域的第一种结构。 整体结构揭示了在DNA的相对侧的头部到尾部时的两种分子。 另外,我们解决了与相同元素结合的人LRH-1 DNA结合结构域的结构。 我们探索了通过这两个NRS管理Oct4识别的结构元素。 (c)2016 Elsevier有限公司保留所有权利。

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