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 implicated in diverse biological processes, including gametogenesis, embryonic development and embryonal carcinoma cell differentiation. We have examined the binding and regulation of the human orthologue, hGCNF, expressed in the 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 mammalia. The formation of interspecies dimers of the in vitro synthesized proteins suggests that cellular GCNF binding is mediated by homodimers. Both the mouse and the human protein bind in concert with cellular factors to DNA. Treatment of NT2/D1 cells with all-trans retinoic acid (atRA) is accompanied first by an up-regulation followed later by a down-regulation of hGCNF and its mRNA. Temporary up-regulation in NT2/D1 cells after treatment with atRA suggests that hGCNF is important for human neural determination and differentiation.
Schmitz
T P
TP
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany.
Süsens
U
U
Borgmeyer
U
U
D000818:Animals; D019556:COS Cells; D002457:Cell Extracts / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002457:Cell Extracts; D004268:DNA-Binding Proteins; C539950:NR6A1 protein, human; C539954:Nr6a1 protein, mouse; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014212:Tretinoin; D004247:DNA