A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).
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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DOI：
10.1016/j.jmb.2016.10.025
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发表时间：
2016-12-04
影响因子：
5.6
通讯作者：
Ortlund EA
中科院分区：
文献类型：
--
作者：
Weikum ER;Tuntland ML;Murphy MN;Ortlund EA
Oct 4是维持干细胞多能性和自我更新所需的转录因子。在分化之前，Oct 4必须被沉默以允许发育中的胚胎中的三个胚层的发育。这种微调是由核受体，肝受体同系物-1和生殖细胞核因子控制。肝受体同源物-1负责驱动Oct 4的表达，其中生殖细胞核因子在分化时抑制其表达。这两种受体都与位于Oct 4启动子内的DR 0基序结合。在这里，我们提出了第一个结构的小鼠生殖细胞核因子DNA结合域与Oct 4 DR 0的复合物。整体结构显示两个分子以头对尾的方式结合在DNA的相对两侧。此外，我们解决了与相同元件结合的人肝受体同源物-1 DNA结合结构域的结构。我们探讨了这两个核受体对Oct 4识别的结构元件。
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, liver receptor homolog-1 and germ cell nuclear factor. Liver receptor homolog-1 is responsible for driving the expression of Oct4 where germ cell nuclear factor represses its expression upon differentiation. Both receptors bind to a DR0 motif located within the Oct4 promoter. Here, we present the first structure of mouse germ cell nuclear factor DNA binding domain in complex with the Oct4 DR0. 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 liver receptor homolog-1 DNA binding domain bound to the same element. We explore the structural elements that govern Oct4 recognition by these two nuclear receptors.