Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation.
We have cloned a cDNA encoding the full-length coding region of the human homologue of the germ cell nuclear factor (GCNF)/retinoid receptor-related testis-associated receptor (RTR), from a human testis cDNA library. The amino acid sequence of human GCNF/RTR is highly homologous to that of the mouse GCNF/RTR. The largest difference between the two homologues is a 15 amino acid deletion in the human GCNF/RTR at amino acid 47. The GCNF/RTR gene was localized on human chromosome 9. Northern blot analysis using poly(A)+ RNA from different human tissues showed that GCNF/RTR mRNA is most abundantly expressed in the testis. GCNF/RTR was also highly expressed in embryonic stem cells and embryonal carcinoma cells but repressed in its differentiated derivatives. Induction of differentiation of mouse embryonal carcinoma F9 cells and human embryonal carcinoma NTERA-2 clone D1 (NT2/D1) cells by all-trans retinoic acid was accompanied by a down-regulation of GCNF/RTR. Our observations suggest that GCNF/RTR plays a role in the control of gene expression in early embryogenesis and during spermatogenesis.
Lei
W
W
Cell Biology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Hirose
T
T
Zhang
L X
LX
Adachi
H
H
Spinella
M J
MJ
Dmitrovsky
E
E
Jetten
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D054278:Embryonal Carcinoma Stem Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D018076:DNA, Complementary; 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; D018168:Receptors, Retinoic Acid