The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene.

The EMBO journal ·Vol. 11 ·No. 2 ·1992-02-00 ·Pages 433-9

Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, Green S

Abstract

Peroxisome proliferators are a diverse group of chemicals, including several hypolipidaemic drugs, that activate a nuclear hormone receptor termed the peroxisome proliferator activated receptor (PPAR). The peroxisomal enzyme acyl CoA oxidase (ACO) is the most widely used marker of peroxisome proliferator action. We have examined the 5' flanking region of the rat ACO gene for sequences that mediate the transcriptional effect of peroxisome proliferators and have identified an element located 570 bp upstream of the ACO gene that confers responsiveness to the hypolipidaemic peroxisome proliferator Wy-14,643. This peroxisome proliferator response element (PPRE) contains a direct repeat of the sequence motifs TGACCT and TGTCCT and binds PPAR. These data therefore indicate an important role of PPAR in mediating the action of peroxisome proliferators including the induction of ACO.

MeSH Terms

Acyl-CoA Oxidase Animals Anticholesteremic Agents/pharmacology Baculoviridae/genetics Base Sequence Binding Sites Cell Line Chloramphenicol O-Acetyltransferase/genetics,metabolism Fatty Acid Desaturases/genetics Humans Kinetics Methylation Microbodies/drug effects,physiology,ultrastructure Molecular Sequence Data Oligodeoxyribonucleotides Oxidoreductases/genetics Plasmids Promoter Regions, Genetic Pyrimidines/pharmacology Rats Repetitive Sequences, Nucleic Acid Transfection

Chemicals

Anticholesteremic Agents Oligodeoxyribonucleotides Pyrimidines pirinixic acid Oxidoreductases Fatty Acid Desaturases Acyl-CoA Oxidase Chloramphenicol O-Acetyltransferase

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Tugwood J D

Imperial Chemical Industries PLC, Macclesfield, Cheshire, UK.

Issemann I

Anderson R G

Bundell K R

McPheat W L

Green S

References (30)

30 references, click to expand

Steroid receptor family: structure and functions.
Endocr Rev. 1990 May;11(2):201-20 PMID: 2194782
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
Nature. 1990 Oct 18;347(6294):645-50 PMID: 2129546
Differences between the promoting activities of the peroxisome proliferator WY-14,643 and phenobarbital in rat liver.
Cancer Res. 1989 Jun 15;49(12):3246-51 PMID: 2566380
Formation of 8-hydroxydeoxyguanosine in liver DNA of rats following long-term exposure to a peroxisome proliferator.
Cancer Res. 1989 May 15;49(10):2603-5 PMID: 2713844
Nuclear receptors enhance our understanding of transcription regulation.
Trends Genet. 1988 Nov;4(11):309-14 PMID: 2853466
Isolation and structural characterization of the rat acyl-CoA oxidase gene.
J Biol Chem. 1987 Jun 15;262(17):8138-43 PMID: 3036801
Structural organization of the gene for rat enoyl-CoA hydratase:3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme.
J Biol Chem. 1987 Jun 15;262(17):8144-50 PMID: 3036802
The steroid and thyroid hormone receptor superfamily.
Science. 1988 May 13;240(4854):889-95 PMID: 3283939
Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.
Proc Natl Acad Sci U S A. 1986 Mar;83(6):1747-51 PMID: 3456610
An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells.
Cell. 1986 Sep 26;46(7):1053-61 PMID: 3463433
Baculovirus expression vectors: the requirements for high level expression of proteins, including glycoproteins.
J Gen Virol. 1987 May;68 ( Pt 5):1233-50 PMID: 3553425
High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study.
J Cell Biol. 1969 Dec;43(3):506-20 PMID: 4900611
Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans.
Crit Rev Toxicol. 1983;12(1):1-58 PMID: 6360536
Factors influencing peroxisome proliferation in cultured rat hepatocytes.
Arch Toxicol. 1984 Oct;55(4):239-46 PMID: 6517701
A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug.
Proc Natl Acad Sci U S A. 1976 Jun;73(6):2043-6 PMID: 180535
Two cis-acting regulatory sequences in the peroxisome proliferator-responsive enhancer region of rat acyl-CoA oxidase gene.
Biochem Biophys Res Commun. 1991 Mar 29;175(3):866-71 PMID: 2025260
Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene.
Nature. 1990 Jan 11;343(6254):177-80 PMID: 2153268
Rat peroxisomal 3-ketoacyl-CoA thiolase gene. Occurrence of two closely related but differentially regulated genes.
J Biol Chem. 1990 Mar 15;265(8):4600-6 PMID: 2307679
Biochemical mechanisms of induction of hepatic peroxisome proliferation.
Annu Rev Pharmacol Toxicol. 1989;29:145-63 PMID: 2658768
The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element.
DNA. 1989 Sep;8(7):503-16 PMID: 2766932
Isolation, complementary DNA sequence, and regulation of rat hepatic lauric acid omega-hydroxylase (cytochrome P-450LA omega). Identification of a new cytochrome P-450 gene family.
J Biol Chem. 1987 Jan 15;262(2):801-10 PMID: 3027069
Relationship of hepatic peroxisome proliferation and replicative DNA synthesis to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) in rats.
Cancer Res. 1988 Dec 1;48(23):6739-44 PMID: 3180084
A versatile in vivo and in vitro eukaryotic expression vector for protein engineering.
Nucleic Acids Res. 1988 Jan 11;16(1):369 PMID: 3340539
The estrogen-responsive element as an inducible enhancer: DNA sequence requirements and conversion to a glucocorticoid-responsive element.
EMBO J. 1987 Dec 1;6(12):3719-27 PMID: 3480798
Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor.
EMBO J. 1986 Sep;5(9):2231-6 PMID: 3780678
The effect of hypolipidemic agents on the hepatic microsomal drug-metabolizing enzyme system of the rat. Induction of cytochrome(s) P-450 with specificity toward terminal hydroxylation of lauric acid.
Drug Metab Dispos. 1982 Mar-Apr;10(2):110-5 PMID: 6124394
Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.
Cell. 1991 Jun 28;65(7):1255-66 PMID: 1648450
A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.
Cell. 1991 Aug 9;66(3):555-61 PMID: 1651173
Peroxisome proliferation and nongenotoxic carcinogenesis: commentary on a symposium.
Fundam Appl Toxicol. 1991 Feb;16(2):233-48 PMID: 2055355
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875

Article Info

Journal

The EMBO journal

Abbr.

EMBO J

ISSN

0261-4189

Published

1992-02-00

Pages

433-9

Language

English

Region

England

NLM ID

8208664

PMCID

PMC556472

Subset

External Links

PubMed source PMC Full Text View journal details

Analysis Services

The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene.

Contact

WeChat Official Account