The Histone Variant MacroH2A Interferes with Transcription Factor Binding and SWI/SNF Nucleosome Remodeling

• Published in: Molecular cell 2003-04, Vol.11 (4), p.1033-1041
• Main Authors: Angelov, Dimitar, Molla, Annie, Perche, Pierre-Yves, Hans, Fabienne, Côté, Jacques, Khochbin, Saadi, Bouvet, Philippe, Dimitrov, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites - genetics; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Eukaryotic Cells - metabolism; Genes, Regulator - genetics; Histones - genetics; Histones - metabolism; Humans; NF-kappa B - genetics; NF-kappa B - metabolism; Nucleosomes - genetics; Nucleosomes - metabolism; Protein Structure, Tertiary - genetics; Repressor Proteins - genetics; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(03)00100-X

The unusual histone variant macroH2A (mH2A) has been associated with repression of transcription, but the molecular mechanisms by which it exerts this function are unknown. Here we have identified a mechanism by which the different domains of mH2A may be involved in the repression of transcription. Evidence is presented that the presence of mH2A in a positioned nucleosome interferes with the binding of the transcription factor NF-κB. The nonhistone region of mH2A was identified to be associated with this interference. Importantly, the presence of macroH2A was found to severely impede SWI/SNF nucleosome remodeling and movement to neighboring DNA segments. This property of mH2A was demonstrated to reside only in its H2A-like domain. A hypothesis explaining the role of histone variants in transcriptional regulation is proposed.