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Epigenetic determination of a cell‐specific gene expression program by ATF‐2 and the histone variant macroH2A
Author(s) -
Agelopoulos Marios,
Thanos Dimitris
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601364
Subject(s) - biology , epigenetics , histone , gene expression , genetics , regulation of gene expression , gene , microbiology and biotechnology , chromatin
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.