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J. Biol. Chem., Vol. 278, Issue 52, 52401-52405, December 26, 2003

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The Secreted Frizzled Related Protein 2 (SFRP2) Gene Is a Target of the Pax2 Transcription Factor^*

Patrick D. Brophy, Katherine M. Lang¶, and Gregory R. Dressler¶||

From the Pediatrics and ^¶Pathology, University of Michigan, Ann Arbor, Michigan 48109

Despite their essential role in vertebrate development, the function of Pax proteins in gene regulation is not well understood. To identify potential genes regulated by the Pax2 protein, we screened embryonic kidney cells transformed with Pax2-expressing retroviruses for genes activated in response to Pax2 expression. In this system, the gene encoding the secreted frizzled related protein, Sfrp2, was strongly activated in all Pax2b-expressing cells. This activation of Sfrp2 expression correlated with changes in chromatin structure at the Sfrp2 locus, particularly in and around regions of Pax2 binding. Although the amount of Pax2-dependent transactivation was low in transient assays, the data suggests that local alterations of chromatin structure by Pax proteins can greatly enhance expression when presented in the right cellular context.

Received for publication, May 28, 2003 , and in revised form, September 23, 2003.

^* This work was supported in part by National Institutes of Health Grants DK54740 and DK54723 and a Polycystic Kidney Disease Foundation grant-in-aid (to G. R. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement^TM in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

A recipient of the American Society of Nephrology Gottschalk Award and supported in part by a fellowship from the Polycystic Kidney Research Foundation.

^|| To whom correspondence should be addressed: Dept. of Pathology, Univ. of Michigan, 1150 W. Medical Center Dr., Ann Arbor, MI 48109. Tel.: 734-764-6490; E-mail: dressler{at}umich.edu.

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