Specialization of the chromatin remodeler RSC to mobilize partially-unwrapped nucleosomes

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.

Specialization of the Chromatin Remodeler RSC to Mobilize Partially-Unwrapped Nucleosomes

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.

An Optimized In Silico Neuroinformatics Approach

A computationally optimized molecular analysis into the cell-fate regulations from embryonic development is one of the unexplored zones in human neurogenic field. It is governed by SOX11 (Sex determining regions-Y bOX-11) protein domain's interaction with DNA. In the present study, 3D monomer of the responsible domain of SOX11 was constructed, simulated and analyzed. Residues indulged with DNA interaction were examined. The observed conserved residue, Arg3 and Arg16 in the wild-type SOX11-DNA interaction were mutated with Ala3 and Ala16. Mutated SOX11-HMG protein sequence was re-modeled and optimized. Residue-level alteration on DNA interaction was examined. On mutation, stability of the proteins (on DNA interaction) and protein-DNA complexes were discerned via energy-calculating parameters, solvent-accessibility area, electrostatic surface-potential and conformational switching, with supportive statistical significance. Therefore, this probe provides an outlook to discern SOX11 to interact firmly with DNA via mutations and thereby perform cell-fate determinations more efficiently.