The Gcn5 bromodomain co-ordinates nucleosome remodelling

The access of transcription factors to eukaryotic promoters often requires modification of their chromatin structure, which is accomplished by the act ion of two general classes of multiprotein complexes(1). One class contains histone acetyltransferases (HATs), such as Gcn5 in the SAGA complex(2), wh ich acetylate nucleosomal histones. The second dass contains ATPases, such as Swi2 in the Swi/Snf complex(3), which provide the energy for nucleosome remodelling. In several promoters these two complexes cooperate but their f unctional linkage is unknown(4-8). A protein module that is present in, all , nuclear HATs, the bromodomain, could provide such a link(9). The recently reported in vitro binding of a HAT bromodomain with acetylated lysines wit hin H3 and H4 aminoterminal peptides(10) indicates that this interaction ma y constitute a targeting step for events that follow histone acetylation. H ere we use a suitable promoter to show that bromodomain residues essential for acetyl-lysine binding are not required in vivo for Gcn5-mediated histon e acetylation but are fundamental for the subsequent Swi2-dependent nucleos ome remodelling and consequent transcriptional activation. We show that the Gcn5 bromodomain stabilizes the Swi/Snf complex on this promoter.