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.

The SWI/SNF complex is required for the expression of many yeast genes. Previous studies have implicated DNA binding transcription activators in targeting SWI/SNF to UASs and promoters. To determine how activators interact with the complex and to examine the importance of these interactions, relative to other potential targeting mechanisms, for SWI/SNF function, we sought to identify and mutate the activator-interaction domains in the complex. Here we show that the N-terminal domain of Snf5 and the second quarter of Swi1 are sites of activation domain contact. Deletion of both of these domains left the SWI/SNF complex intact but impaired its ability to bind activation domains. Importantly, while deletion of either domain alone had minor phenotypic effect, deletion of both resulted in strong SWI/SNF related phenotypes. Thus, two distinct activator-interaction domains play overlapping roles in the targeting activity of SWI/SNF, which is essential for its function in vivo.

The histone regulatory (HIR) and histone promoter control (HPC) repressor proteins regulate three of the four histone gene loci during the Saccharomyces cerevisiae cell cycle. Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 proteins form a stable HIR repressor complex. The HIR complex promotes histone deposition onto DNA in vitro and constitutes a novel nucleosome assembly complex. The HIR complex stably binds to DNA and nucleosomes. Furthermore, HIR complex binding to nucleosomes forms a distinct protein/DNA complex resistant to remodeling by SWI/SNF. Thus, the HIR complex is a novel nucleosome assembly complex which functions with SWI/SNF to regulate transcription. Histone gene transcription is tightly regulated during cell cycle progression and coordinated with DNA replication in eukaryotes. Six of the eight histone genes (HTA1-HTB1, HHT1-HHF1, and HHT2-HHF2) are negatively regulated through a site present in their promoter close to upstream activation sequence (UAS) elements (Osley et al. 1986;Freeman et al. 1992). Histone gene transcription is repressed outside of the G1/S in Saccharomyces cerevisiae. Several trans-acting factors that act at the negative site to repress transcription were identified through genetic screens Xu et al. 1992). Some of these factors, the histone regulatory (HIR) genes including HIR1, HIR2, HIR3, and the histone promoter control (HPC) gene HPC2, are transcriptional corepressors that are not thought to possess intrinsic DNA-binding activity Xu et al. 1992;Sherwood et al. 1993;Lamour et al. 1995). However, both Hir1 and Hir2 associate with the HTA1-HTB1 regulatory domain, although there is no evidence that the Hir proteins bind directly to the cis-acting site required for the repression of the histone genes (Dimova et al. 1999;Sutton et al. 2001). The Hir proteins are postulated to be recruited to the negative site by a yet unidentified sequence-specific binding factor, and once at this site directly repress transcription (Spector et al. 1997;DeSilva et al. 1998). The mechanism by which Hir/Hpc proteins repress histone gene transcription is not clear, but is likely to involve the modulation of chromatin structure. The Hir corepressors interact with the SWI/SNF chromatin-remodeling complex and are required for its recruitment to the HTA1-HTB1 promoter (Dimova et al. 1999).The yeast multisubunit SWI/SNF complex is an ATPdependent chromatin-remodeling complex that can mobilize nucleosomes for activation or repression of a subset of yeast genes (Wang 2003;Lee et al. 2004). The SWI/ SNF complex can be recruited to specific promoters through a variety of mechanisms, one of which is through direct interaction with sequence-specific transcriptional activators. We previously showed that activator-interaction domains within the Snf5 and Swi1 subunits play a critical role in the promoter targeting of SWI/SNF, which is essential for its function in vivo (Prochasson et al. 2003).Deletion analysis of SWI/SNF subunits demonstrates that they are required for maximal expression of the histone ...