Function and Selectivity of Bromodomains in Anchoring Chromatin-Modifying Complexes to Promoter Nucleosomes

Abstract

The functions of the SAGA and SWI/SNF complexes are interrelated and can form stable "epigenetic marks" on promoters in vivo. Here we show that stable promoter occupancy by SWI/SNF and SAGA in the absence of transcription activators requires the bromodomains of the Swi2/Snf2 and Gcn5 subunits, respectively, and nucleosome acetylation. This acetylation can be brought about by either the SAGA or NuA4 HAT complexes. The bromodomain in the Spt7 subunit of SAGA is dispensable for this activity but will anchor SAGA if it is swapped into Gcn5, indicating that specificity of bromodomain function is determined in part by the subunit it occupies. Thus, bromodomains within the catalytic subunits of SAGA and SWI/SNF anchor these complexes to acetylated promoter nucleosomes.

Use of chromatin remodeling ATPases as RNAi targets for parental control of western corn rootworm (Diabrotica virgifera virgifera) and Neotropical brown stink bug (Euschistus heros)

“…Brahma of the SWI2/ SNF2 family of the ATP-dependent remodeling enzymes contains a bromodomain, which binds acetylated histones (Hassan et al, 2002). Similar domain conservation was observed for E. heros (Figure 1A).…”

Mechanisms of ATP dependent chromatin remodeling

“…Histone modifications were however found to effect the interaction of SWI/SNF with nucleosomes. Acetylation by SAGA and NuA4 was found to stabilize SWI/ SNF interaction with nucleosome in a bromodomain dependent manner [49,145]. Acetylation of lysine 8 of histone H4 has also been shown to facilitate recruitment of SWI/SNF [146].…”

“…The ATPase domain consists of seven subdomains that structurally forms two lobes referred to as the DEXD and helicase motifs that form a cleft to which DNA binds based on X-ray crystal structure from the related Rad54 ATPase domain [41,42]. In addition the Swi2/Snf2 protein contains at its Cterminus a bromo domain which has been shown to recognize specific acetylated lysines in histone tails [43][44][45][46][47][48][49][50]. The Swi1 contains an ARID domain (an AT-rich interaction domain) that is found in its orthologs OSA in Drosophila and BAF250 in mammals.…”

Coactivators and general transcription factors have two distinct dynamic populations dependent on transcription

“…Studies in different eukaryotes have suggested that the presence of SAGA at the promoters of genes is needed to facilitate Pol II recruitment and pre‐initiation complex (PIC) formation (Wyce et al , 2007; Nagy et al , 2009; Helmlinger et al , 2011; Lang et al , 2011). The recruitment of SAGA and ATAC coactivator complexes to genomic loci has been suggested to take place by several distinct mechanisms: (i) by activator mediated recruitment (McMahon et al , 1998; Brown et al , 2001; Fishburn et al , 2005; Reeves & Hahn, 2005), (ii) by interactions with basal transcription machinery components (Larschan & Winston, 2001; Laprade et al , 2007; Mohibullah & Hahn, 2008) and (iii) through chromatin‐interacting domains of SAGA and ATAC subunits (Hassan et al , 2002; Vermeulen et al , 2010; Bian et al , 2011; Bonnet et al , 2014). Nevertheless, the dynamics of SAGA and ATAC interactions with chromatin are not yet well understood, as there has been no direct and systematic monitoring of the nuclear mobility of these two co‐activator complexes in live cells.…”