Germ cell nuclear factor is a response element-specific repressor of transcription

Biochemical and Biophysical Research Communications
Austin J CooneyK J Jackson

Abstract

We have shown that the orphan receptor Germ Cell Nuclear Factor (GCNF) binds to a direct repeat of the sequence AGGTCA with zero base pair spacing (DR0). Here, we further characterize the binding characteristics of GCNF. We demonstrate that GCNF binds specifically to DR0s as a homodimer, and does not bind with high affinity to DR1-DR6 sequences. GCNF is the first nuclear receptor shown to bind specifically to DR0s. The wild type GCNF is unable to transactivate the reporter plasmid DR0(2)tkCAT. Lacking a ligand to activate GCNF, we fused the activation domain from the viral protein VP16 to GCNF, and observed activation of DR0(2)tkCAT. This activation is specifc to DR0s, and is not observed when that sequence is replaced by DR1-DR6 sequences. In addition GCNF does not transactivate through an SF-1 response element. At increasing concentrations, wild type GCNF is able to repress basal transcription. Repression is again specific to DR0s. The preference of GCNF for the DR0 sequence both in vitro and in transfections suggests that GCNF defines a novel nuclear receptor signaling pathway.

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Citations

Jan 24, 2009·Biology of Reproduction·Zi-Jian LanAustin J Cooney
Nov 8, 2015·The International Journal of Biochemistry & Cell Biology·Yinfang WangPeng Zhang
Dec 18, 2007·Biochemical and Biophysical Research Communications·Heng ZhangZi-Jian Lan
Nov 13, 2001·Developmental Cell·G FuhrmannA J Cooney
May 6, 2003·Developmental Biology·Guillermo BarretoChristine Dreyer
Nov 9, 2010·Biochemical and Biophysical Research Communications·Susumu TanakaEmmanuel Mignot
Feb 28, 2003·Biology of Reproduction·Genyan YangDeborah A O'Brien
Dec 4, 2003·Molecular Reproduction and Development·Alexandra Zilz, Geoffrey M Cooper
Oct 24, 2017·Journal of Cellular Biochemistry·Sung-Won ParkJae-Hwan Kim
Jul 6, 2004·Molecular Reproduction and Development·Geoffrey C Hummelke, Austin J Cooney
Sep 7, 2005·Human Reproduction Update·Stephanie A Pangas, Aleksandar Rajkovic
Oct 26, 1999·Endocrine Reviews·V Giguère
Sep 7, 2006·The Journal of Biological Chemistry·Moritz HentschkeChristian A Hübner
Nov 30, 2006·Pharmacological Reviews·Gérard BenoitVincent Laudet
Oct 17, 2002·The Journal of Biological Chemistry·Zi-Jian LanAustin J Cooney
Jun 25, 2002·The Journal of Biological Chemistry·Zhijiang YanAnton M Jetten
Feb 6, 2010·Reproductive Biomedicine Online·Maurizio ZuccottiSilvia Garagna

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