| First Author | Weikum ER | Year | 2016 |
| Journal | J Mol Biol | Volume | 428 |
| Issue | 24 Pt B | Pages | 4981-4992 |
| PubMed ID | 27984042 | Mgi Jnum | J:359790 |
| Mgi Id | MGI:6859461 | Doi | 10.1016/j.jmb.2016.10.025 |
| Citation | Weikum ER, et al. (2016) A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1). J Mol Biol 428(24 Pt B):4981-4992 |
| abstractText | 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 DR0 motif located within the Oct4 promoter. Here, we present the first structure of mouse GCNF 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 LRH-1 DNA-binding domain bound to the same element. We explore the structural elements that govern Oct4 recognition by these two NRs. |
