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J. Biol. Chem., Vol. 281, Issue 33, 23922-23931, August 18, 2006

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A Conserved 12-Amino Acid Motif in Sall1 Recruits the Nucleosome Remodeling and Deacetylase Corepressor Complex^*

Shannon M. Lauberth and Michael Rauchman¹

From the Departments of Biochemistry and Molecular Biology and Internal Medicine, Veterans Affairs Medical Center, Saint Louis University, St. Louis, Missouri 63106

Sall1 is a multi-zinc finger transcription factor that represses gene expression and regulates organogenesis. In this report, we further characterize the domain of Sall1 necessary for repression. We show that endogenous Sall1 binds to the nucleosome remodeling and deacetylase corepressor complex (NuRD) and confirm the functionality of the Sall1-associating macromolecular complex by showing that the complex possesses HDAC activity. NuRD is involved in global transcriptional repression and regulation of specific developmental processes. The mechanism by which sequence-specific DNA-binding proteins associate with NuRD is not well understood. We have identified a highly conserved 12-amino acid motif in the transcription factor Sall1 that is sufficient for the recruitment of NuRD. Single amino acid substitutions defined the critical amino acid peptide motif as RRKQXK-PXXF. This motif probably exhibits a more general role in regulating gene expression, since other proteins containing this domain, including all Sall family members and an unrelated zinc finger protein Ebfaz, mediate transcriptional repression and associate with NuRD. These results also have important implications for the pathogenesis of Townes-Brocks, a syndrome caused by SALL1 mutations.

Received for publication, December 19, 2005 , and in revised form, May 8, 2006.

^* This work was supported by National Institutes of Health Grant DK067222 (to M. R.) and a Veterans Affairs Merit Award (to M. R.). 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" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: St. Louis Veterans Affairs Medical Center, 657/111B-JC, 915 N. Grand Blvd., St. Louis, MO 63106. Tel.: 314-289-6485; Fax: 314-289-7012; E-mail: rauchman{at}slu.edu.

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