The binding of a Fos/Jun heterodimer can completely disrupt the structure of a nucleosome.

An important first step in the chromatin remodelling process is the initial binding of a transcriptional activator to a nucleosomal template. We have investigated the ability of Fos/Jun (a transcriptional activator involved in the signal transduction pathway) to interact with its cognate binding site located in the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when this site was reconstituted into a nucleosome. Two different nucleosome assembly systems were employed to assemble principally non-acetylated or acetylated nucleosomes. The ability of Fos/Jun to interact with an acetylated or an unacetylated nucleosome differed markedly. Fos/Jun bound to an unacetylated nucleosome with only a 4- to 5-fold reduction in DNA binding affinity compared with naked DNA. Strikingly, the binding of Fos/Jun to a single high-affinity site incorporated into an acetylated nucleosome resulted in the complete disruption of nucleosomal structure without histone displacement. Moreover, this disruption was sufficient to facilitate the subsequent binding of a second transcription factor.