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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:对孤儿核受体,生殖细胞核因子(GCNF)和肝受体同源物1(LRH-1)进行Oct4调控的结构研究。

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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是在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,必须沉默Oct4以允许发育中的胚中三个胚层的发育。这种微调是由核受体(NRs),肝受体同系物1(LRH-1)和生殖细胞核因子(GCNF)控制的。肝受体同源物1负责驱动Oct4的表达,而GCNF在分化时会抑制其表达。两种受体均与位于Oct4启动子内的DRO基序结合。在这里,我们介绍与Oct4 DRO复杂的小鼠GCNF DNA结合结构域的第一个结构。整体结构揭示了两个分子以头对尾的方式结合在DNA的相对两侧。此外,我们解决了与同一元件结合的人LRH-1 DNA结合结构域的结构。我们探索了控制这两个NR识别Oct4的结构要素。 (C)2016 Elsevier Ltd.保留所有权利。

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