Germ cell nuclear factor: an orphan receptor with unexpected properties

1998 ◽  
Vol 76 (12) ◽  
pp. 800-810 ◽  
Author(s):  
Holger Greschik ◽  
R. Schüle
Keyword(s):  
Germ Cell ◽  
Orphan Receptor ◽  
Nuclear Factor ◽  
Germ Cell Nuclear Factor

scholarly journals Germ Cell Nuclear Factor: An Orphan Receptor in Search of a Function

1999 ◽  
Vol 39 (4) ◽  
pp. 796-806 ◽  
Author(s):  
AUSTIN J. COONEY ◽  
DEBORAH KATZ ◽  
GEOFFREY C. HUMMELKE ◽  
KATHY J. JACKSON
Keyword(s):  
Germ Cell ◽  
Orphan Receptor ◽  
Nuclear Factor ◽  
Germ Cell Nuclear Factor

scholarly journals Characterization of the DNA-Binding and Dimerization Properties of the Nuclear Orphan Receptor Germ Cell Nuclear Factor

1999 ◽  
Vol 19 (1) ◽  
pp. 690-703 ◽  
Author(s):  
Holger Greschik ◽  
Jean-Marie Wurtz ◽  
Philip Hublitz ◽  
Fabian Köhler ◽  
Dino Moras ◽  
...  
Keyword(s):  
Dna Binding ◽  
Germ Cell ◽  
Nuclear Receptor ◽  
Target Gene ◽  
Binding Domain ◽  
Orphan Receptor ◽  
Nuclear Factor ◽  
Binding Behavior ◽  
Helix 12 ◽  
Germ Cell Nuclear Factor

ABSTRACT The orphan receptor germ cell nuclear factor (GCNF) is a member of the superfamily of nuclear receptors. During development, GCNF exhibits a restricted brain-specific expression pattern, whereas GCNF expression in the adult is germ cell specific. Therefore, the receptor may participate in the regulation of neurogenesis and reproductive functions. No natural GCNF target gene has yet been identified, but recent data demonstrate specific and high-affinity binding of GCNF either to the direct repeat DNA element AGGTCAAGGTCA (DR0) or to extended half-sites, such as TCAAGGTCA. In this study, we show that murine GCNF (mGCNF) can bind as a homodimer to extended half-sites, thus describing a novel property within the nuclear receptor superfamily. Homodimeric binding to extended half-sites requires the presence of a dimerization function within the mGCNF DNA-binding domain (DBD) and a novel dimerization surface encompassing the putative helix 3 and the helix 12 region of the mGCNF ligand-binding domain (LBD). In addition, the mGCNF LBD has the potential to adopt different conformations with distinct dimerization properties. The helix 12 region of the mGCNF LBD not only regulates the switch between these dimerization conformations but also dictates the DNA-binding behavior and transcriptional properties of the different dimerization conformations. In summary, our findings describe unique DNA-binding and dimerization properties of a nuclear receptor and suggest a novel mechanism that allows mGCNF to modulate target gene activity.

scholarly journals Loss of Orphan Receptor Germ Cell Nuclear Factor Function Results in Ectopic Development of the Tail Bud and a Novel Posterior Truncation

2001 ◽  
Vol 21 (2) ◽  
pp. 663-677 ◽  
Author(s):  
Arthur C.-K. Chung ◽  
Deborah Katz ◽  
Fred A. Pereira ◽  
Kathy J. Jackson ◽  
Francesco J. DeMayo ◽  
...  
Keyword(s):  
Germ Cell ◽  
Nuclear Receptor ◽  
Germ Line ◽  
Physiological Role ◽  
Orphan Receptor ◽  
Marker Genes ◽  
Nuclear Factor ◽  
Orphan Nuclear Receptor ◽  
Embryonic Survival ◽  
Germ Cell Nuclear Factor

ABSTRACT The dynamic embryonic expression of germ cell nuclear factor (GCNF), an orphan nuclear receptor, suggests that it may play an important role during early development. To determine the physiological role of GCNF, we have generated a targeted mutation of theGCNF gene in mice. Germ line mutation of theGCNF gene proves that the orphan nuclear receptor is essential for embryonic survival and normal development. GCNF−/− embryos cannot survive beyond 10.5 days postcoitum (dpc), probably due to cardiovascular failure. Prior to death, GCNF−/− embryos suffer significant defects in posterior development. Unlike GCNF+/+ embryos, GCNF−/− embryos do not turn and remain in a lordotic position, the majority of the neural tube remains open, and the hindgut fails to close. GCNF−/− embryos also suffer serious defects in trunk development, specifically in somitogenesis, which terminates by 8.75 dpc. The maximum number of somites in GCNF−/− embryos is 13 instead of 25 as in the GCNF+/+ embryos. Interestingly, the tailbud of GCNF−/− embryos develops ectopically outside the yolk sac. Indeed, alterations in expression of multiple marker genes were identified in the posterior of GCNF−/− embryos, including the primitive streak, the node, and the presomitic mesoderm. These results suggest that GCNF is required for maintenance of somitogenesis and posterior development and is essential for embryonic survival. These results suggest that GCNF regulates a novel and critical developmental pathway involved in normal anteroposterior development.

cDNA cloning of two closely related forms of human germ cell nuclear factor (GCNF)

1997 ◽  
Vol 1352 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Marcus Kapelle ◽  
Jörn Krätzschmar ◽  
Manfred Husemann ◽  
Wolf-Dieter Schleuning
Keyword(s):  
Germ Cell ◽  
Cdna Cloning ◽  
Nuclear Factor ◽  
Germ Cell Nuclear Factor
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