|
Originally published In Press as doi:10.1074/jbc.M300319200 on February 21, 2003
J. Biol. Chem., Vol. 278, Issue 18, 15473-15483, May 2, 2003
Characterization of the Human Lung CYP2F1 Gene and
Identification of a Novel Lung-specific Binding Motif*
Brian A.
Carr ,
Jie
Wan ,
Ronald N.
Hines§, and
Garold S.
Yost ¶
From the Department of Pharmacology and Toxicology,
University of Utah, Salt Lake City, Utah 84112 and
§ Department of Pediatrics, Medical College of Wisconsin,
Milwaukee, Wisconsin 53226-4801
The CYP2F1 gene encodes a cytochrome
P450 enzyme capable of bioactivating a number of pulmonary-selective
toxicants. The expression of CYP2F1 is highly
tissue-selective; the highest expression is observed in the lung with
little or no hepatic expression. The objective of these studies was to
elucidate the mechanisms that govern the unique tissue-specific
regulation of CYP2F1. Cosmid and bacterial artificial
chromosome clones were screened and sequenced to identify a gene that
spanned 14 kbp containing 10 exons, including an untranslated exon 1. Primer extension analysis and 5'-rapid amplification of cDNA ends
were used to identify the transcription start site. Several sequences
homologous to known cis-elements were identified in the
5'-upstream region of the CYP2F1 promoter. Transient
transfection studies with luciferase reporter constructs demonstrated a
significant functional lung cell-specific CYP2F1 promoter
region (from position 129 to +115). DNase footprinting analysis of
1.6 kbp of the upstream sequence with nuclear extracts from human lung
tissues revealed one strong DNA-protein complex at 152 to 182. This
nuclear protein (called lung-specific factor, LSF) was present only in
lung but not liver or heart tissues. Competitive electrophoretic
mobility shift assays characterized a DNA consensus site, within the
LSF-binding domain, that was highly similar to two E box motifs, but no
known "E box" trans-factors were identified. These
studies identified a novel LSF and its consensus sequence that may
control tissue-specific expression of CYP2F1.
*
This work was supported by NHLBI Grant HL60143 from the
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) NM_000774.
¶
To whom correspondence should be addressed: Dept. of
Pharmacology and Toxicology, 30 S. 2000 E., Rm. 201, University of
Utah, Salt Lake City, UT 84112. Tel.: 801-581-7956; Fax: 801-585-3945; E-mail: gyost@pharm.utah.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. S. Biggs, J. Wan, N. S. Cutler, J. Hakkola, P. Uusimaki, H. Raunio, and G. S. Yost
Transcription Factor Binding to a Putative Double E-Box Motif Represses CYP3A4 Expression in Human Lung Cells
Mol. Pharmacol.,
September 1, 2007;
72(3):
514 - 525.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Ling, Y. Wei, and X. Ding
Transcriptional Regulation of Human CYP2A13 Expression in the Respiratory Tract by CCAAT/Enhancer Binding Protein and Epigenetic Modulation
Mol. Pharmacol.,
March 1, 2007;
71(3):
807 - 816.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Girault, N. Rougier, C. Chesne, R. Lidereau, P. Beaune, I. Bieche, and I. de Waziers
SIMULTANEOUS MEASUREMENT OF 23 ISOFORMS FROM THE HUMAN CYTOCHROME P450 FAMILIES 1 TO 3 BY QUANTITATIVE REVERSE TRANSCRIPTASE-POLYMERASE CHAIN REACTION
Drug Metab. Dispos.,
December 1, 2005;
33(12):
1803 - 1810.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Zhang, Q.-Y. Zhang, D. Liu, T. Su, Y. Weng, G. Ling, Y. Chen, J. Gu, B. Schilling, and X. Ding
EXPRESSION OF CYTOCHROME P450 AND OTHER BIOTRANSFORMATION GENES IN FETAL AND ADULT HUMAN NASAL MUCOSA
Drug Metab. Dispos.,
October 1, 2005;
33(10):
1423 - 1428.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Wan, B. A. Carr, N. S. Cutler, D. L. Lanza, R. N. Hines, and G. S. Yost
SP1 AND SP3 REGULATE BASAL TRANSCRIPTION OF THE HUMAN CYP2F1 GENE
Drug Metab. Dispos.,
August 1, 2005;
33(8):
1244 - 1253.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Ling, C. R. Hauer, R. M. Gronostajski, B. T. Pentecost, and X. Ding
Transcriptional Regulation of Rat CYP2A3 by Nuclear Factor 1: IDENTIFICATION OF A NOVEL NFI-A ISOFORM, AND EVIDENCE FOR TISSUE-SELECTIVE INTERACTION OF NFI WITH THE CYP2A3 PROMOTER IN VIVO
J. Biol. Chem.,
July 2, 2004;
279(27):
27888 - 27895.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|