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J Biol Chem, Vol. 275, Issue 2, 759-768, January 14, 2000

An Alu Element from the K18 Gene Confers Position-independent Expression in Transgenic Mice*

David A. WilloughbyDagger §, Adrian Vilaltapar , and Robert G. OshimaDagger **

From the Dagger  Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92037 and the  Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California 90033

We have identified a 323-base pair fragment of the 5'-flanking sequence of the K18 gene, which confers position-independent and copy number-dependent expression on two heterologous transgenes. This fragment is composed primarily of an Alu repetitive element. Its activity in mice is correlated with its RNA polymerase III promoter activity and its orientation-dependent ability to inhibit potential transcriptional interference in a transfection assay. However, the activity of the Alu element is not correlated with its enhancer blocking activity, a characteristic of insulator elements. In addition, this Alu element did not block the suppressive effect of co-injecting mouse alpha  satellite DNA with the transgene. This Alu element is likely responsible for at least part of the protective effects of the sequences flanking the K18. These results suggest that transcriptionally active Alu elements may eliminate transcriptional interference of neighboring genes. This Alu element is one component of the locus control region associated with the K18 gene. Other Alu repetitive elements may also function to define regulatory domains.

* This work was supported by Public Health Service Grant CA42302 (to R. G. O.) and Cancer Center Support Grant CA30199 from the National Cancer Institute.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.

§ Supported in part by National Research Service Award F32 CA69823 from the National Cancer Institute.

par Present address: Vical Inc., 9373 Towne Center Dr., Suite 100, San Diego, CA 92121-3088.

** To whom correspondence should be addressed: Burnham Inst., 10901 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: 858-646-3100; Fax: 858-646-3193; E-mail: rgoshima@burnham-inst.org.

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