Article
- The EMBO Journal (2006) 25, 4843 - 4853
- doi:10.1038/sj.emboj.7601364
Published online: 12 October 2006
Subject Categories:
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
Correspondence to:
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
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
