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: E Vilain, W Guo, Y H Zhang, E R McCabe
• Journal: Biochemical and molecular medicine (Biochem Mol Med) Vol. 61 Issue 1 Pg. 1-8 (Jun 1997) ISSN: 1077-3150 [Print] United States
• PMID: 9232190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DAX-1 Orphan Nuclear Receptor
• DNA-Binding Proteins
• Fushi Tarazu Transcription Factors
• Homeodomain Proteins
• NR0B1 protein, human
• NR5A1 protein, human
• Receptors, Cytoplasmic and Nuclear
• Receptors, Retinoic Acid
• Repressor Proteins
• Steroidogenic Factor 1
• Transcription Factors

Topics

• Adrenocortical Carcinoma (genetics, metabolism)
• Base Sequence
• DAX-1 Orphan Nuclear Receptor
• DNA-Binding Proteins (drug effects, genetics, metabolism, pharmacology)
• Fushi Tarazu Transcription Factors
• Gene Expression Regulation (drug effects)
• Genes, Reporter
• Homeodomain Proteins
• Humans
• Molecular Sequence Data
• Polymerase Chain Reaction
• Promoter Regions, Genetic
• Receptors, Cytoplasmic and Nuclear
• Receptors, Retinoic Acid (drug effects, genetics, metabolism)
• Repressor Proteins
• Sequence Deletion
• Steroidogenic Factor 1
• Transcription Factors (drug effects, genetics, metabolism, pharmacology)
• Transfection
• Tumor Cells, Cultured