Alternative titles; symbols
HGNC Approved Gene Symbol: CYP8B1
Cytogenetic location: 3p22.1 Genomic coordinates (GRCh38) : 3:42,872,192-42,875,879 (from NCBI)
Sterol 12-alpha-hydroxylase (CYP8B1) is a hepatic cytochrome P450 that controls the ratio of cholic acid over chenodeoxycholic acid in bile and thus controls the solubility of cholesterol (summary by Gafvels et al., 1999).
From rabbit liver, Eggertsen et al. (1996) cloned a cDNA, which they termed CYP12, coding for sterol 12-alpha-hydroxylase. Northern blot analysis revealed that CYP12 is expressed exclusively in human and rabbit liver tissue. Fasting of rats and mice increased CYP12 enzyme activity and mRNA levels.
Gafvels et al. (1999) obtained cDNAs encoding human and mouse CYP8B1. The deduced 501-amino acid human CYP8B1 protein is approximately 75% identical to the mouse and rabbit proteins. It contains a hydrophobic, membrane-spanning N terminus and conserved oxygen-binding, steroidogenic, and heme-binding segments. Northern blot analysis revealed expression of a 3.9-kb CYP8B1 transcript in liver. In mouse, expression was restricted to liver.
Zhang and Chiang (2001) showed that hepatocyte nuclear factor-4-alpha (HNF4A; 600281) strongly activates CYP8B1 promoter activity, whereas CYP7A promoter-binding factor (CPF, or NR5A2; 604453) has much less effect. The promoter activities were strongly repressed by bile acid. EMSA and site-directed mutagenesis analysis indicated that HNF4A, CPF, and the bile acid response element have overlapping binding sites in CYP8B1. Mammalian 2-hybrid analysis demonstrated interaction of HNF4A with the small heterodimer partner (SHP; 604630). Functional analysis determined that SHP represses HNF4A-induced CYP8B1 transcription. Zhang and Chiang (2001) concluded that bile acids repress human CYP8B1 transcription by reducing the transactivation activity of HNF4A through the interaction of HNF4A with SHP and a reduction of HNF4A expression in liver.
By PCR and genomic sequence analyses, Gafvels et al. (1999) determined that the CYP8B1 gene lacks introns. Primer extension and database analyses indicated that the promoter region of CYP8B1 contains multiple regulatory motifs, including a possible TATA box 51 bp from the transcriptional start site.
By FISH and radiation hybrid analysis, Gafvels et al. (1999) mapped the CYP8B1 gene to chromosome 3p22-p21.3. They mapped the mouse gene to chromosome 9qF4
Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.-I., Bjorkhem, I. Molecular cloning and expression of rabbit sterol 12-alpha-hydroxylase. J. Biol. Chem. 271: 32269-32275, 1996. [PubMed: 8943286] [Full Text: https://doi.org/10.1074/jbc.271.50.32269]
Gafvels, M., Olin, M., Chowdhary, B. P., Raudsepp, T., Andersson, U., Persson, B., Jansson, M., Bjorkhem, I., Eggertsen, G. Structure and chromosomal assignment of the sterol 12-alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns. Genomics 56: 184-196, 1999. [PubMed: 10051404] [Full Text: https://doi.org/10.1006/geno.1998.5606]
Zhang, M., Chiang, J. Y. L. Transcriptional regulation of the human sterol 12-alpha-hydroxylase gene (CYP8B1): roles of hepatocyte nuclear factor 4-alpha in mediating bile acid repression. J. Biol. Chem. 276: 41690-41699, 2001. [PubMed: 11535594] [Full Text: https://doi.org/10.1074/jbc.M105117200]