Abstract
ISWI family chromatin remodelers typically organize nucleosome arrays, while SWI/SNF family remodelers (RSC) typically disorganize and eject nucleosomes, implying an antagonism that is largely unexplored in vivo. Here, we describe two independent genetic screens for rsc suppressors that yielded mutations in the promoter-focused ISW1a complex or mutations in the 'basic patch' of histone H4 (an epitope that regulates ISWI activity), strongly supporting RSC-ISW1a antagonism in vivo. RSC and ISW1a largely co-localize, and genomic nucleosome studies using rsc isw1 mutant combinations revealed opposing functions: promoters classified with a nucleosome-deficient region (NDR) gain nucleosome occupancy in rsc mutants, but this gain is attenuated in rsc isw1 double mutants. Furthermore, promoters lacking NDRs have the highest occupancy of both remodelers, consistent with regulation by nucleosome occupancy, and decreased transcription in rsc mutants. Taken together, we provide the first genetic and genomic evidence for RSC-ISW1a antagonism and reveal different mechanisms at two different promoter architectures.
Highlights
Genomic DNA is packaged into chromatin, a dynamic material that exhibits numerous changes in post-translational modifications, composition, and protein interactions
This broad separation in function can be partially illustrated by studies of individual chromatin remodelers and their effects on gene expression (Angus-Hill et al, 2001; Fazzio et al, 2001; Vary et al, 2003); in general, remodelers associated with chromatin disassembly promote DNA access and gene expression, while remodelers associated with chromatin organization more often repress gene expression, though there are exceptions to this simplified view
Chromatin remodelers represent a set of complexes with different functional roles; some remodelers are primarily involved in transcriptional activation, while others are more dedicated to chromatin assembly and/or transcriptional repression
Summary
Genomic DNA is packaged into chromatin, a dynamic material that exhibits numerous changes in post-translational modifications, composition, and protein interactions. Certain chromatin remodelers align with these two general categories: those that restrict DNA access by chromatin assembly and organization and those that promote DNA access by chromatin disassembly and disorganization This broad separation in function can be partially illustrated by studies of individual chromatin remodelers and their effects on gene expression (Angus-Hill et al, 2001; Fazzio et al, 2001; Vary et al, 2003); in general, remodelers associated with chromatin disassembly promote DNA access and gene expression, while remodelers associated with chromatin organization more often repress gene expression, though there are exceptions to this simplified view (e.g., increased accessibility can promote repressor access to chromatin). The SWI/SNF family of chromatin remodelers provides a well-studied example of remodelers associated with nucleosome disorganization and/or disassembly. The RSC chromatinremodeling complex is an essential and abundant paralog of the canonical SWI/SNF remodeler (Cairns et al, 1996). The central subunit of RSC, Sth, is a DNA-dependent ATPase that translocates
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