title: DAX1 gene expression upregulated by steroidogenic factor 1 in an adrenocortical carcinoma cell line.
abstract: Two nuclear hormone receptor superfamily members, DAX1 and SF1, are required for normal adrenal cortical development. Mutations in DAX1 are responsible for X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism. Steroidogenic Factor 1 (SF1) regulates the expression of a number of steroidogenic genes and a putative SF1 response element (SF1-RE) in the DAX1 promoter which binds SF1 specifically. Therefore, we examined deletions in the DAX1 promoter driving expression of beta-galactosidase, with and without coexpression of SF1, in the human adrenocortical carcinoma cell line NCI-H295. We defined the DAX initiation start site and localized the putative SF1-RE at -135 to -143 bp. Loss of the putative SF1-RE region or specific removal of the 9-bp SF1 site resulted in decreased transcriptional activity by 2.3-to 2.5-fold. When cotransfected with 1550 bp of the DAX1 promoter, an SF1-containing expression vector increased the transcriptional activity of the DAX1 promoter by 4-fold. No significant change above baseline occurred when the cells were cotransfected with the 1541-bp fragment containing the entire 1550-bp promoter region minus the 9-bp SF1-RE. We conclude that the SF1-RE is an enhancer element within the DAX1 promoter and speculate that SF1 may be a transcription factor that acts, at least in part, through DAX1 for normal adrenal cortical development.
authors.affiliation: Department of Pediatrics, University of California Los Angeles School of Medicine 90095-1752, USA.
authors.forename: E
authors.initials: E
authors.lastname: Vilain
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: E R
authors.initials: ER
authors.lastname: McCabe
mesh_terms: D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D017384:Sequence Deletion; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors