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Nucleic Acids Research Advance Access published online on March 5, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp116
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gene Regulation, Chromatin and Epigenetics

Nucleosome eviction from MHC class II promoters controls positioning of the transcription start site

Elisa Leimgruber1, Queralt Seguín-Estévez1, Isabelle Dunand-Sauthier1, Natalia Rybtsova1, Christoph D. Schmid2,3, Giovanna Ambrosini2,3, Philipp Bucher2,3 and Walter Reith1,*

1Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel-Servet, CH-1211, Geneva, 2Swiss Institute of Bioinformatics, EPFL, CH-1015, Lausanne and 3Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland

*To whom correspondence should be addressed. Tel: +41 22 379 56 66; Fax: +41 22 379 57 46; Email: walter.reith{at}unige.ch

Received December 3, 2008. Revised February 6, 2009. Accepted February 10, 2009.

Nucleosome depletion at transcription start sites (TSS) has been documented genome-wide in multiple eukaryotic organisms. However, the mechanisms that mediate this nucleosome depletion and its functional impact on transcription remain largely unknown. We have studied these issues at human MHC class II (MHCII) genes. Activation-induced nucleosome free regions (NFR) encompassing the TSS were observed at all MHCII genes. Nucleosome depletion was exceptionally strong, attaining over 250-fold, at the promoter of the prototypical HLA-DRA gene. The NFR was induced primarily by the transcription factor complex that assembles on the conserved promoter-proximal enhancer situated upstream of the TSS. Functional analyses performed in the context of native chromatin demonstrated that displacing the NFR without altering the sequence of the core promoter induced a shift in the position of the TSS. The NFR thus appears to play a critical role in transcription initiation because it directs correct TSS positioning in vivo. Our results provide support for a novel mechanism in transcription initiation whereby the position of the TSS is controlled by nucleosome eviction rather than by promoter sequence.


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[Abstract] [Full Text] [PDF]


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