About this item:

172 Views | 158 Downloads

Author Notes:

Corresponding author: eortlun@emory.edu, Phone: 404-727-5014, 1510 Clifton Road NE, Rollins Research Center G235, Atlanta, GA 30322.

Conceived and designed experiments: ERW MLT EAO.

Performed the experiments ERW MLT MNM EAO.

Analyzed the data ERW MLT EAO.

Contributed to writing the manuscript ERW MLT EAO.

X-ray data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory.

Supporting institutions may be found at www.ser-cat.org/members/html.

Subject:

Research Funding:

Use of the Advanced Photon source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • nuclear receptors
  • X-ray crystallography
  • germ cell nuclear factor
  • liver receptor homolog-1
  • Oct4 regulation
  • DNA-BINDING DOMAIN
  • TRANSCRIPTION FACTOR
  • RESPONSE ELEMENT
  • GENE-EXPRESSION
  • COMPLEX
  • PROTEIN
  • RECOGNITION
  • CLONING
  • FTZ-F1

A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1)

Tools:

Journal Title:

Journal of Molecular Biology

Volume:

Volume 428, Number 24

Publisher:

, Pages 4981-4992

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2016 Elsevier Ltd

Export to EndNote