Structural highlights
Function
[NR6A1_MOUSE] Orphan nuclear receptor. Binds to a response element containing the sequence 5'-TCAAGGTCA-3'. May be involved in the regulation of gene expression in germ cell development during gametogenesis.[1]
Publication Abstract from PubMed
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.
A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF) and Liver Receptor Homolog-1 (LRH-1).,Weikum ER, Tuntland ML, Murphy MN, Ortlund EA J Mol Biol. 2016 Oct 27. pii: S0022-2836(16)30451-X. doi:, 10.1016/j.jmb.2016.10.025. PMID:27984042[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen F, Cooney AJ, Wang Y, Law SW, O'Malley BW. Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol. 1994 Oct;8(10):1434-44. PMID:7854358 doi:http://dx.doi.org/10.1210/mend.8.10.7854358
- ↑ Weikum ER, Tuntland ML, Murphy MN, Ortlund EA. 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. 2016 Oct 27. pii: S0022-2836(16)30451-X. doi:, 10.1016/j.jmb.2016.10.025. PMID:27984042 doi:http://dx.doi.org/10.1016/j.jmb.2016.10.025