EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Down-regulation of the rat hepatic sterol 27-hydroxylase gene by bile acids in transfected primary hepatocytes: possible role of hepatic nuclear factor 1alpha


Down-regulation of the rat hepatic sterol 27-hydroxylase gene by bile acids in transfected primary hepatocytes: possible role of hepatic nuclear factor 1alpha



Journal of Steroid Biochemistry and Molecular Biology 70(1-3): 1-14



ISSN/ISBN: 0960-0760

PMID: 10528998

DOI: 10.1016/s0960-0760(99)00099-0

In vitro and in vivo studies have shown that the sterol 27-hydroxylase (CYP27) gene is transcriptionally repressed by hydrophobic bile acids. The molecular mechanism(s) of repression of CYP27 by bile acids is unknown. To identify the bile acid responsive element (BARE) and transcription factor(s) that mediate the repression of CYP27 by bile acids, constructs of the CYP27 5'-flanking DNA were linked to either the CAT or luciferase reporter gene and transiently transfected into primary rat hepatocytes. Taurocholate (TCA), taurodeoxycholate (TDCA) and taurochenodeoxycholate (TCDCA) significantly reduced CAT activities of the -840/+23, -329/+23, and -195/+23 mCAT constructs. A -76/+23 construct showed no regulation by bile acids. When a DNA fragment (-110/-86) from this region was cloned in front of an SV 40 promoter it showed down-regulation by TDCA. 'Super'-electrophoretic mobility shift assays (EMSA) indicated that both HNF1alpha and C/EBP bind to the -110 to -86 bp DNA fragment. Recombinant rat HNF1alpha and C/EBPalpha competitively bound to this DNA fragment. 'Super'-EMSA showed that TDCA addition to hepatocytes in culture decreased HNF1alpha, but not C/EBP, binding to the -110/-86 bp DNA fragment. A four base pair substitution mutation (-103 to -99) in this sequence eliminated TCA and TDCA regulation of the (-840/+23) construct. The substitution mutation also eliminated (>95%) HNF1alpha, but not C/EBP, binding to this DNA fragment. We conclude that bile acids repress CYP27 transcription through a putative BARE located between -110 and -86 bp of the CYP27 promoter. The data suggest that bile acids repress CYP27 transcriptional activity by decreasing HNF1alpha binding to the CYP27 promoter.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010496412

Download citation: RISBibTeXText

Related references

The negative effects of bile acids and tumor necrosis factor-alpha on the transcription of cholesterol 7alpha-hydroxylase gene (CYP7A1) converge to hepatic nuclear factor-4: a novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors. Journal of Biological Chemistry 276(33): 30708-30716, 2001

The negative effects of bile acids and tumor necrosis factor-a on the transcription of cholesterol 7a-hydroxylase gene (CYP7A1) converge to hepatic nuclear factor-4. A novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors. The Journal of Biological Chemistry 276(33): 708-16, 2001

Regulation of human sterol 27-hydroxylase gene by bile acids and hepatocyte nuclear factor 4alpha. Gene (Amsterdam) 313: 71-82, 14 August, 2003

Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha). Gene 313: 71-82, 2003

Transcriptional regulation of hepatic sterol 27-hydroxylase by bile acids. American Journal of Physiology 270(4 Pt 1): G646-G652, 1996

Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase gene transcription. Hepatology 21(2): 501-510, 1995

Regulation of glucose-6-phosphatase gene expression in cultured hepatocytes and H4IIE cells by short-chain fatty acids: role of hepatic nuclear factor-4alpha. Journal of Biological Chemistry 278(42): 40694-40701, 2003

Hepatocyte nuclear factor 4alpha plays important roles in transcriptional regulation of human sterol 12alpha-hydroxylase gene by bile acids and circadian rhythm. Hepatology 36(4 Part 2): 241A, 2002

Comparative regulation of hepatic sterol 27-hydroxylase and cholesterol 7alpha-hydroxylase activities in the rat, guinea pig, and rabbit: effects of cholesterol and bile acids. Metabolism: Clinical and Experimental 48(12): 1542-1548, 1999

Regulation of bile acid synthesis in the rat: relationship between hepatic cholesterol 7 alpha-hydroxylase activity and portal bile acids. Journal of Lipid Research 36(2): 315-321, 1995

The regulation of cholesterol 7 alpha hydroxylase activity and protein mass by the hepatic flux of 7 alpha hydroxylated bile acids. Hepatology 12(4 Part 2): 1000, 1990

The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional regulation of the pdx-1 gene. Journal of Biological Chemistry 276(51): 47775-47784, 2001

Transcriptional regulation of cholesterol 7 alpha-hydroxylase mRNA by conjugated bile acids in primary cultures of rat hepatocytes. Journal of Biological Chemistry 268(19): 13987-13993, 1993

Structural aspects of bile acids involved in the regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase. European Journal of Biochemistry 228(3): 596-604, 1995

Transcriptional regulation of the human sterol 12a-hydroxylase gene (CYP8B1). Roles of hepatocyte nuclear factor 4a in mediating bile acid repression. The Journal of Biological Chemistry 276(45): 690-9, 2001