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Originally published In Press as doi:10.1074/jbc.M005468200 on July 11, 2000

J. Biol. Chem., Vol. 275, Issue 41, 31567-31572, October 13, 2000
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Duplicated Downstream Enhancers Control Expression of the Human Apolipoprotein E Gene in Macrophages and Adipose Tissue*

Shyh-Jen ShihDagger §, Charles AllanDagger §||, Sharon GrehanDagger §, Elizabeth TseDagger , Cathal MoranDagger **, and John M. TaylorDagger §Dagger Dagger §§

From the Dagger  Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100 and the § Cardiovascular Research Institute and the Dagger Dagger  Department of Physiology, University of California, San Francisco, California 94143

Two distal enhancers that specify apolipoprotein (apo) E gene expression in isolated macrophages and adipose tissue were identified in transgenic mice that were generated with constructs of the human apoE/C-I/C-I'/C-IV/C-II gene cluster. One of these enhancers, multienhancer 1, consists of a 620-nucleotide sequence located 3.3 kilobases (kb) downstream of the apoE gene. The second enhancer, multienhancer 2, is a 619-nucleotide sequence located 15.9 kb downstream of the apoE gene and 5.9 kb downstream of the apoC-I gene. The two enhancers are 95% identical in sequence, and they are likely to have arisen as a consequence of the gene duplication event that yielded the apoC-I gene and the apoC-I' pseudogene. Both enhancer sequences appear to have equivalent activity in directing apoE gene expression in peritoneal macrophages and in adipocytes, suggesting that their activity in specific cell types may be determined by common regulatory elements.

* This work was supported in part by National Institutes of Health Grant HL37063 (to J. M. T.).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.

Current address: University of California, Davis Cancer Center, Sacramento, CA 95817.

|| Current address: Dept. of Medicine (DO6), University of Sydney, Sydney, New South Wales 2006, Australia.

** Current address: Dept. of Pharmacology, National University of Ireland, Galway, Ireland.

§§ To whom correspondence should be addressed: The J. David Gladstone Institutes, P. O. Box 419100, San Francisco, CA 94141-9100. Tel.: 415-826-7500; Fax: 415-285-5632; E-mail: jtaylor@gladstone.ucsf.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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