Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression.
The cytochrome P450 steroid hydroxylases are coordinately regulated by steroidogenic factor 1 (SF-1), a protein expressed selectively in steroidogenic cells. Based on its expression in steroidogenic tissues and DNA-binding specificity, we isolated a putative SF-1 cDNA from an adrenocortical cDNA library. As evidence that this cDNA encodes SF-1, we now show that it is selectively expressed in steroidogenic cells, that an antiserum against its protein product specifically abolishes the SF-1-related gel-shift complex, and that its coexpression increases promoter activity of the 21-hydroxylase 5'-flanking region in transfection experiments. Sequence analyses of the SF-1 cDNA revealed that it is the mouse homolog of fushi tarazu factor I (FTZ-F1), a nuclear receptor that regulates the fushi tarazu homeobox gene in Drosophila. A second FTZ-F1 homolog, embryonal long terminal repeat-binding protein (ELP), was recently isolated from embryonal carcinoma cells. SF-1 and ELP cDNAs are virtually identical for 1017 base pairs, including putative DNA-binding domains, but diverge at their 5'- and 3'-ends. One genomic clone contained both SF-1- and ELP-specific sequences, confirming their origin from a single gene. Characterization of this gene defined shared exons encoding common regions and alternative promoters and 3'-exons leading to differences between the two FTZ-F1 transcripts. We used in situ hybridization with transcript-specific probes to study the ontogeny of SF-1 and ELP expression. ELP transcripts were not detected from embryonic day 8 to adult, consistent with its previous isolation from embryonal carcinoma cells and its postulated role in early embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS)
Ikeda
Y
Y
Department of Medicine, Duke University Medical Center Durham, North Carolina 27710.
Lala
D S
DS
Luo
X
X
Kim
E
E
Moisan
M P
MP
Parker
K L
KL
D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D005091:Exons; D051717:Fushi Tarazu Transcription Factors; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics*; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase