Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2

Absence of a phenobarbital-responsive enhancer module in the upstream region of the CYP2B18 gene

Midori Yamamoto, Masashi Mise, Sanae Matsumoto, Shoich Ito, Noriko Gohyama, Satoru Ishida, Yasuhiro Sagara, Curtis John Omiecinski, Kazuta Oguri, Hideyuki Yamada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Potential mechanisms were investigated whereby CYP2B18, a cytochrome P450 gene exhibiting high constitutive expression but only low levels of phenobarbital-inducibility in the guinea pig liver, may be differentially regulated versus the highly inducible rat CYP2B2 gene. To comparatively assess potential regulatory sequences associated with CYP2B18, a guinea pig genomic library was screened enabling isolation of the CYP2B18 gene. The genomic screening process resulted in the identification of at least four closely-related CYP2B18 genes, designated here as CYP2B18A-D. Of these isolates, CYP2B18A exhibited sequence identical to that of the CYP2B18 cDNA. Further, the deduced amino acid sequence of the CYP2B18 cDNA was identical to that of N-terminal and internally-derived peptide sequences obtained in this investigation from CYP2B18 protein isolated from guinea pig liver. Genomic structural sequences were derived for CYP2B18A, together with the respective 5′-upstream and intronic regions of the gene. Comparison of the CYP2B18A and CYP2B2 gene sequences revealed the lack of repetitive LINE gene sequences in CYP2B18A, putative silencing elements that effect neighboring genes, although these sequences were present in both 5′-upstream and 3′-downstream regions of CYP2B2. We determined that the phenobarbital-responsive enhancer module was absent from the 5′-upstream region as well as the intronic regions of CYP2B18A gene. We hypothesize that the compromised phenobarbital inducibility of CYP2B18A stems from its lack of a functional phenobarbital responsive enhancer module.

Original languageEnglish (US)
Pages (from-to)124-130
Number of pages7
JournalJournal of Biochemical and Molecular Toxicology
Volume18
Issue number3
DOIs
StatePublished - Aug 26 2004

Fingerprint

Phenobarbital
Rats
Guinea Pigs
Complementary DNA
Genes
Liver
Transcriptional Silencer Elements
steroid 16-beta-hydroxylase
Genomic Library
Cytochrome P-450 Enzyme System
Amino Acid Sequence
Screening
Amino Acids
Peptides

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Yamamoto, Midori ; Mise, Masashi ; Matsumoto, Sanae ; Ito, Shoich ; Gohyama, Noriko ; Ishida, Satoru ; Sagara, Yasuhiro ; Omiecinski, Curtis John ; Oguri, Kazuta ; Yamada, Hideyuki. / Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2 : Absence of a phenobarbital-responsive enhancer module in the upstream region of the CYP2B18 gene. In: Journal of Biochemical and Molecular Toxicology. 2004 ; Vol. 18, No. 3. pp. 124-130.
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Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2 : Absence of a phenobarbital-responsive enhancer module in the upstream region of the CYP2B18 gene. / Yamamoto, Midori; Mise, Masashi; Matsumoto, Sanae; Ito, Shoich; Gohyama, Noriko; Ishida, Satoru; Sagara, Yasuhiro; Omiecinski, Curtis John; Oguri, Kazuta; Yamada, Hideyuki.

In: Journal of Biochemical and Molecular Toxicology, Vol. 18, No. 3, 26.08.2004, p. 124-130.

Research output: Contribution to journalArticle

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T1 - Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2

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AU - Yamamoto, Midori

AU - Mise, Masashi

AU - Matsumoto, Sanae

AU - Ito, Shoich

AU - Gohyama, Noriko

AU - Ishida, Satoru

AU - Sagara, Yasuhiro

AU - Omiecinski, Curtis John

AU - Oguri, Kazuta

AU - Yamada, Hideyuki

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