The Gcn5 bromodomain co-ordinates nucleosome remodelling

Abstract

The access of transcription factors to eukaryotic promoters often requires modification of their 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, which acetylate nucleosomal histones. The second class contains ATPases, such as Swi2 in the Swi/Snf complex, which provide the energy for nucleosome remodelling. In several promoters these two complexes cooperate but their functional linkage is unknown. A protein module that is present in all nuclear HATs, the bromodomain, could provide such a link. The recently reported in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides indicates that this interaction may constitute a targeting step for events that follow histone acetylation. Here we use a suitable promoter to show that bromodomain residues essential for acetyl-lysine binding are not required in vivo for Gcn5-mediated histone acetylation but are fundamental for the subsequent Swi2-dependent nucleosome remodelling and consequent transcriptional activation. We show that the Gcn5 bromodomain stabilizes the Swi/Snf complex on this promoter.

Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1

“…Also shown are anti-GST Western blots of the whole cell lysates used for immunoprecipitation between components of SAGA and SWI/SNF, suggesting a functional relationship between these complexes (Pollard and Peterson, 1997;Roberts and Winston, 1997;Sterner et al, 1999). It has also been shown that acetylation of the N-terminal tails of histones can modify SWI/SNF function and processivity (Logie et al, 1999), and additional genetic and biochemical interactions between SAGA and SWI/ SNF have been reported (Cosma et al, 1999;Hassan et al, 2001;Krebs et al, 2000;Syntichaki et al, 2000). If E1A were acting here simply to ablate SAGA or SWI/SNF function, then the reported synthetic lethality observed in double mutants of SWI/SNF and SAGA would lead to the prediction that expression of E1A in cells containing single mutations that disrupt either complex, would cause death.…”

Putative Arabidopsis Transcriptional Adaptor Protein (PROPORZ1) is required to modulate histone acetylation in response to auxin

“…Next to its role in histone acetylation, yeast SAGA orchestrates additional chromatin remodeling activities and recruitment of components of the core transcriptional machinery (30)(31)(32)(33)(34). PRZ1 could be required for coordination of such interdependent processes in Arabidopsis, determining crosstalk between histone acetylation and auxin- controlled gene expression.…”

When the SWI/SNF complex remodels … the cell cycle

“…It is therefore possible that after facilitating the recruitment of E2F, the SWI/SNF complex also plays an active role in preventing this transcription factor from mediating activation. What determines the activating or the repressing e ect of the SWI/SNF complex remains unclear, but the e ect of the complex seems to be dependent on the presence of the histone tails and on their state of acetylation Logie et al, 1999;Syntichaki et al, 2000). Furthermore, both Brg1 and Brm contain a Bromodomain.…”