DNA binding, protein interaction and differential expression of the human germ cell nuclear factor

The mouse germ cell nuclear factor (mGCNF) is an orphan nuclear receptor im plicated in diverse biological processes, including gametogenesis, embryoni c development and embryonal carcinoma cell differentiation. We have examine d the binding and regulation of the human orthologue, hGCNF, expressed in t he teratocarcinoma-derived cell line NTera-2/clone D1 (NT2/D1). Binding of GCNF to the direct repeat of the sequence -AGGTCA- (DR-0) is conserved in m ammalia. The formation of interspecies dimers of the in vitro synthesized p roteins suggests that cellular GCNF binding is mediated by homodimers. Both the mouse and the human protein bind in concert with cellular factors to D NA. Treatment of NT2/D1 cells with all-trans retinoic acid (atRA) is accomp anied first by an up-regulation followed later by a down-regulation of hGCN F and its mRNA. Temporary up-regulation in NT2/D1 cells after treatment wit h atRA suggests that hGCNF is important for human neural determination and differentiation. (C) 1999 Elsevier Science B.V. All rights reserved.