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 in itial binding of a transcriptional activator to a nucleosomal template , We have investigated the ability of Fos/Jun (a transcriptional activ ator 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 i nto a nucleosome, Two different nucleosome assembly systems were emplo yed to assemble principally non-acetylated or acetylated nucleosomes. The ability of Fos/Jun to interact with an acetylated or an unacetylat ed nucleosome differed markedly. Fos/Jun bound to an unacetylated nucl eosome with only a 4- to 5-fold reduction in DNA binding affinity comp ared with naked DNA, Strikingly, the binding of Fos/Jun to a single hi gh-affinity site incorporated into an acetylated nucleosome resulted i n the complete disruption of nucleosomal structure without histone dis placement, Moreover, this disruption was sufficient to facilitate the subsequent binding of a second transcription factor.