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J. Biol. Chem., Vol. 283, Issue 17, 11078-11082, April 25, 2008
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¶1
From the
Programs in
Genetics and ¶Immunology and the
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111
The ubiquitously expressed TFII-I family of multifunctional transcription factors is involved in gene regulation as well as signaling. Despite the fact that they share significant sequence homology, these factors exhibit varied and distinct functions. The lack of knowledge about its binding sites and physiological target genes makes it more difficult to assign a definitive function for the TFII-I-related protein, BEN. We set out to determine its optimal binding site with the notion of predicting its physiological target genes. Here we report the identification of an optimal binding sequence for BEN by SELEX (systematic evolution of ligands by exponential enrichment) and confirm the relevance of this sequence by functional assays. We further performed a data base search to assign genes that have this consensus site(s) and validate several candidate genes by quantitative PCR upon stable silencing of BEN and by chromatin immunoprecipitation assay upon stable expression of BEN. Given that haploinsufficiency in BEN is causative to Williams-Beuren syndrome, these results may further lead to the identification of a set of physiologically relevant target genes for BEN and may help identify molecular determinants of Williams-Beuren syndrome.
Received for publication, February 29, 2008 , and in revised form, March 6, 2008.
* This work was supported by the National Institutes of Health Grant HD04603. 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.
The on-line version of this article (available at http://www.jbc.org) contains two supplemental tables.
1 To whom correspondence should be addressed: Tufts University School of Medicine, 150 Harrison Ave., Boston MA 02111. Tel.: 617-636-6715; Fax: 617-636-2990; E-mail: ananda.roy{at}tufts.edu.
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