Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 52, Pages 22257-22262Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0909511106
Keywords
nucleosome statistical ordering; chromatin-mediated gene regulation; physical modeling; atomic force microscopy
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Funding
- Conseil Regional Rhone-Alpes
- Agence Nationale de la Recherche [ANR-06-PCVI-0026]
- Agence Nationale de la Recherche (ANR) [ANR-06-PCVI-0026] Funding Source: Agence Nationale de la Recherche (ANR)
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Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in the collective organization of nucleosomes in vivo than previously thought. Yet in living cells, this organization also results from the action of various external factors like DNA-binding proteins and chromatin remodelers. To decipher the code for intrinsic chromatin organization, there is thus a need for in vitro experiments to bridge the gap between computational models of nucleosome sequence preferences and in vivo nucleosome occupancy data. Here we combine atomic force microscopy in liquid and theoretical modeling to demonstrate that a major sequence signaling in vivo are high-energy barriers that locally inhibit nucleosome formation rather than favorable positioning motifs. We show that these genomic excluding-energy barriers condition the collective assembly of neighboring nucleosomes consistently with equilibrium statistical ordering principles. The analysis of two gene promoter regions in Saccharomyces cerevisiae and the human genome indicates that these genomic barriers direct the intrinsic nucleosome occupancy of regulatory sites, thereby contributing to gene expression regulation.
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