Teleost FTZ-F1 homolog and its splicing variant determine the expression of the salmon gonadotropin IIbeta subunit gene.
Steroidogenic factor 1, a member of the fushi tarazu factor 1 (FTZ-F1) subfamily of nuclear receptors, is a key regulator in mammalian reproduction. From an embryonic complementary DNA library, the zebrafish homolog of FTZ-F1 (zFF1A) and an alternatively spliced variant (zFF1B) were isolated. zFF1B represented a C-terminally truncated version of zFF1A. Whole mount in situ hybridization and reverse transcriptase-PCR analysis revealed that both zFF1A and B transcripts were present in the developing pituitaries, adult fish brain, gonads, and liver, albeit zFF1B messenger RNA was absent in testis. Comparison of the primary sequences of zFF1 with those of other FTZ-F1 subfamily members showed a close structural relationship between the mouse liver receptor homolog, which activated the alpha1-fetoprotein gene in rodent liver. However, similar to mouse steroidogenic factor 1, zFF1A regulated chinook salmon gonadotropin IIbeta subunit gene expression. On the contrary, zFF1B, which could bind a consensus gonadotrope-specific element with an affinity similar to that of zFF1A, lacked both the trans-activation function and synergistic interaction with the estrogen receptor. Furthermore, cotransfection studies in HeLa cells showed that zFF1B was a strong competitor for the action of zFF1A on the chinook salmon gonadotropin IIbeta subunit gene promoter. Our investigation suggests that 1) zFF1 represents an ancestor protein of the vertebrate FTZ-F1 homologs; 2) the antagonistic relationship between zFF1A and -B may dictate the expression of the FTZ-F1 target genes in a variety of tissues, including the pituitary; and 3) the naturally occurring zFF1B provides evidence that the C-terminal portion of zFF1A (80 amino acid residues) contains a major trans-activation function and a protein-protein interface.
Liu
D
D
Hospital for Sick Children, Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Le Drean
Y
Y
Ekker
M
M
Xiong
F
F
Hew
C L
CL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006065:Gonadotropins, Pituitary / Q000737:chemistry / Q000235:genetics*; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D010053:Ovary / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D012474:Salmon / Q000235:genetics*; D016415:Sequence Alignment; D054339:Steroidogenic Factor 1; D013737:Testis / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D006065:Gonadotropins, Pituitary; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; C515056:NR5A2 protein, zebrafish; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C515058:steroidogenic factor 1, mouse