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J. Biol. Chem., Vol. 282, Issue 13, 9445-9457, March 30, 2007

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Chromatin Remodeling by SWI/SNF Results in Nucleosome Mobilization to Preferential Positions in the Rat Osteocalcin Gene Promoter^*

José Gutiérrez, Roberto Paredes, Fernando Cruzat, David A. Hill, Andre J. van Wijnen, Jane B. Lian, Gary S. Stein, Janet L. Stein, Anthony N. Imbalzano, and Martin Montecino¹

From the Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Barrio Universitario s/n, Casilla 160-C, Concepcion 4079100, Chile and the Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Changes in local chromatin structure accompany transcriptional activation of eukaryotic genes. In vivo these changes in chromatin organization can be catalyzed by ATP-dependent chromatin-remodeling complexes, such as SWI/SNF. These complexes alter the tight wrapping of DNA in the nucleosomes and can facilitate the mobilization of the histone octamer to adjacent DNA segments, leaving promoter regulatory elements exposed for transcription factor binding. To gain understanding of how the activity of SWI/SNF complexes may be modulated by the different DNA sequences within a natural promoter, we have reconstituted nucleosomes containing promoter segments of the transcriptionally active cell type-specific osteocalcin (OC) gene and determined how they affect the directional movements of the nucleosomes. Our results indicate that SWI/SNF complexes induce octamer sliding to preferential positions in the OC promoter, leading to a nucleosomal organization that resembles that described in intact cells expressing the OC gene. Our studies demonstrate that the position of the histone octamer is primarily determined by sequences within the OC promoter that include or exclude nucleosomes. We propose that these sequences are critical components of the regulatory mechanisms that mediate expression of this tissue-specific gene.

Received for publication, October 19, 2006 , and in revised form, February 1, 2007.

^* This work was supported by the Fondo Nacional de Desarrollo Cientifico y Tecnológico (Grants 1030479 to M. M. and 2990066 to J. G.), by Comisión Nacional de Investigacion Cientifica y Tecnológica-Programa Bicentenario de Ciencia y Tecnológia (Grant ACT-044 to M. M.), by National Institutes of Health (NIH) Grant GM56244 (to A. N. I.), and by NIH-Fogarty International Research Collaboration Award Grant 5RO3TW00990 (to M. M. and G. S.). 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. Tel.: 56-41-220-3815; Fax: 56-41-223-9687; E-mail: mmonteci{at}udec.cl.

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