|
 |
|
|
| 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 |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHEngineering Oncolytic Measles Virus to Circumvent the Intracellular Innate Immune Response Molecular Therapy Original Article The EMBO Journal Article Roles of histone acetylation and chromatin remodeling factor in a meiotic recombination hotspot The EMBO Journal Article (21 Apr 2004) Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 Nature Structural & Molecular Biology Article (01 Apr 2006) |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |