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Article
Subject Categories: Chromatin & Transcription | Immunology
The EMBO Journal (2006) 25, 4843–4853, doi:10.1038/sj.emboj.7601364
Published online 12 October 2006
Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A
Marios Agelopoulos and Dimitris Thanos
Institute of Molecular Biology and Genetics, Biomedical Sciences Research Center 'Al. Fleming', Vari, Athens, Greece

To whom correspondence should be addressed
Dimitris Thanos, Present address: Institute of Molecular Biology, Genetics and Biotechnology, Foundation for Biomedical Research of the Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece. Tel.: +30 210 6597244; Fax: +30 210 6597545; E-mail: thanos@bioacademy.gr or dt73@columbia.edu

Received 6 April 2006; Accepted 31 August 2006; Published online 12 October 2006.
Abstract
Transcriptional activation of the interleukin-8 (IL-8) gene is restricted to distinct cell types, although the transcriptional regulatory proteins controlling IL-8 gene expression are ubiquitous. We show that cell-specific transcription of IL-8 is due to the distinct chromatin architecture on the enhancer/promoter before the arrival of the inducing signal. In expressing epithelial cells the enhancer/promoter is nucleosome-free, whereas in non-expressing B cells a nucleosome masks the entire regulatory region. The B-cell-specific nucleosome contains the histone variant macroH2A, which is responsible for preventing transcription factor binding. Recruitment of the repressive macroH2A nucleosome requires direct interactions between ATF-2 bound to the nearby AP1 site and macroH2A and it is regulated by DNA-induced protein allostery. siRNA against ATF-2 or macroH2A rescues IL-8 transcription in B cells. Thus, a transcription factor can work as a transcriptional repressor by orchestrating and maintaining the assembly of specialized local chromatin architectures.
Keywords: transcription factors, chromatin structure, gene expression, histone variants, protein allostery
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