Transcriptional activation in eucaryotes often requires modification
of chromatin structure which is accomplished by the action of two
general classes of multiprotein complexes. One class contains histone
acetyltransferases (HATs), such as Gcn5 in the SAGA complex, that
acetylate nucleosomal histones. The second class contains ATPases,
such as Swi2 in the Swi/Snf complex, which provide the energy for
nucleosome remodeling. In a number of promoters these two complexes
co-operate but their functional linkage is unknown. A protein module
present in all nuclear HATs, the bromodomain, could provide for such a
link. The recently reported in vitro binding of a HAT
bromodomain with acetylated lysines within H3 and H4 N-terminal
peptides, suggests that this interaction constitutes a targeting step
for events that follow histone acetylation. In order to address this
possibility we have developed a suitable promoter that directs SAGA
and Swi/Snf dependent transcriptional activation, in yeast. We have
shown that Swi/Snf functions only following Gcn5 dependent acetylation
of nucleosomes and that bromodomain-residues essential for
acetyl-lysine binding are not required in vivo for this
acetylation but are fundamental for the subsequent Swi2-dependent
nucleosome remodeling. In fact, we have demonstrated that the
independently recruited Swi/Snf complex is destabilized by the Gcn5
mediated histone acetylation and the bromodomain counteracts this
effect.
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