Abstract
SWI/SNF-family chromatin remodeling complexes, such as S. cerevisiae RSC, slide and eject nucleosomes to regulate transcription. Within nucleosomes, stiff DNA sequences confer spontaneous partial unwrapping, prompting whether and how SWI/SNF-family remodelers are specialized to remodel partially-unwrapped nucleosomes. RSC1 and RSC2 are orthologs of mammalian PBRM1 (polybromo) which define two separate RSC sub-complexes. Remarkably, in vitro the Rsc1-containing complex remodels partially-unwrapped nucleosomes much better than does the Rsc2-containing complex. Moreover, a rsc1Δ mutation, but not rsc2Δ, is lethal with histone mutations that confer partial unwrapping. Rsc1/2 isoforms both cooperate with the DNA-binding proteins Rsc3/30 and the HMG protein, Hmo1, to remodel partially-unwrapped nucleosomes, but show differential reliance on these factors. Notably, genetic impairment of these factors strongly reduces the expression of genes with wide nucleosome-deficient regions (e.g., ribosomal protein genes), known to harbor partially-unwrapped nucleosomes. Taken together, Rsc1/2 isoforms are specialized through composition and interactions to manage and remodel partially-unwrapped nucleosomes.
Highlights
Nucleosomes regulate transcription in diverse ways and can either block or attract transcriptional regulators (Workman and Kingston, 1998; Iyer, 2012)
Rsc1 and Rsc2 are highly similar proteins (45% identical, 62% similar), with high homology present in the bromodomains, bromodomainadjacent homology (BAH) domain, and the CT1 region – whereas the CT2 region, which is required for Rsc1 or Rsc2 assembly into RSC, is considerably more divergent (Cairns et al, 1999)
We began by exploring whether these Rsc1- or Rsc2-containing subtypes differ in composition, beyond Rsc1/2 themselves
Summary
Nucleosomes regulate transcription in diverse ways and can either block or attract transcriptional regulators (Workman and Kingston, 1998; Iyer, 2012). SWI/SNF-family ATP-dependent chromatin remodeling complexes (CRCs) have evolved to conduct nucleosome sliding and ejection, and enable transcription factor access to DNA. These CRCs are complex in both composition and mechanism; they utilize a catalytic ATPase to translocate DNA around nucleosomes to conduct nucleosome sliding and eviction, and contain an additional set of proteins to help target and regulate each complex (Clapier and Cairns, 2009; Lorch and Kornberg, 2017; Narlikar et al, 2013). RSC complex (like others in the SWI/SNF family) is found in more than one compositional subtype, and contains either Rsc or its highly-related paralog, Rsc (Cairns et al, 1999). RSC1 and RSC2 are redundant for viability (rsc1D rsc2D mutants are inviable), loss of only one confers
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