Nucleic Acids Research, 1990, Vol. 18, No. 14 4237-4242
© 1990
MOLECULAR BIOLOGY |
Glucocorticoid regulation of a phenobarbital-inducible cytochrome P-450 gene: the presence of a functional glucocorticoid response element in the 5'-flanking region of the CYP2B2 gene
Department of Cell Biology and The Kaplan Cancer Center, New York University School of Medicine New York, NY 10016, USA
*To whom correspondence should be addressed
Received December 13, 1989. Revised May 23, 1990. Accepted May 23, 1990.
The rat cytochrome P450 CYP2B2 gene encodes one of the two major phenobarbital-inducible forms of hepatic microsomal cytochrome P-450. The sequence of a 1.4 Kb DNA segment from the 5' flanking region of this region [Jaiswal, A., Rivkin, E. and Adesnik, M. Nucl. Acids. Res. 75: 6755 (1987)] reveals the presence of a pentadecameric oligonucleotide sequence, located approximately 1.3 Kb upstream of the transcription initiation site, which is highly similar to the sequences of glucocorticoid response elements (GREs) that mediate the hormone-dependent transcriptional activation of many other genes. The putative GRE in the CYP2B2 gene 5' flanking region is shown to be functional by demonstrating that segments of DNA that contain it, including one that is only 25bp long, are capable of conferring dexamethasone inducibility on a chloramphenicol acetyltransfer-ase gene whose transcription is driven by the Herpes virus thymidine kinase gene promoter. Moreover, binding of a protein contained in a rat liver nuclear extract to a 25 bp synthetic DNA segment that contains the putative GRE was demonstrated in a gel mobility shift assay. This binding was specifically competed away by a DNA segment that contains the murine mammary tumor virus long terminal repeat which encompasses several well characterized GRE elements. The implications of these findings for the in vivo regulation of the P450IIB2 gene by glucocorticoids are discussed.
+Present address: La Jolla Cancer Research Foundation, 1091 North Torrey Pines Road, La Jolla, CA 92037, USA
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