Electrostatic Interactions between Arginines and the Minor Groove in the Nucleosome

Abstract

Proteins rely on a variety of readout mechanisms to preferentially bind specific DNA sequences. The nucleosome offers a prominent example of a shape readout mechanism where arginines insert into narrow minor groove regions that face the histone core. Here we compare DNA shape and arginine recognition of three nucleosome core particle structures, expanding on our previous study by characterizing two additional structures, one with a different protein sequence and one with a different DNA sequence. The electrostatic potential in the minor groove is shown to be largely independent of the underlying sequence but is, however, dominated by groove geometry. Our results extend and generalize our previous observation that the interaction of arginines with narrow minor grooves plays an important role in stabilizing the deformed DNA in the nucleosome.

Probing DNA shape and methylation state on a genomic scale with DNase I

“…Recently, an observed correlation between these two variables was interpreted as influence of nucleosome positioning on methylation patterning (45). However, electrostatic interactions between arginines and the minor groove occur in the nucleosome (22,47), and the minor groove narrowing associated with cytosine methylation could enhance these. The methylation patterns might therefore also be a partial determinant of nucleosome position, with methylated CpG dinucleotides giving rise to stronger electrostatic interactions with histones, increasing the stability of nucleosomes.…”

Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability inSaccharomyces cerevisiae

“…Studies have suggested that sprocket arginine-DNA contacts may play an important role in the rotational positioning of nucleosomes (Luger et al 1997;Harp et al 2000;Rohs et al 2009;Wang et al 2010;West et al 2010). For example, short poly(A) stretches narrow the DNA minor groove, potentially enhancing electrostatic interactions between the DNA phosphate backbone and the sprocket arginine (Rohs et al 2009;West et al 2010).…”

“…Sprocket arginine residues are highly conserved (Muthurajan et al 2003;Sullivan and Landsman 2003), and the insertion of sprocket arginine side chains into the DNA minor groove comprises a significant fraction of the solvent accessible surface area that is buried upon histone-DNA binding (Davey et al 2002). Studies have suggested that sprocket arginine-DNA contacts may play an important role in the rotational positioning of nucleosomes (Luger et al 1997;Harp et al 2000;Rohs et al 2009;Wang et al 2010;West et al 2010). For example, short poly(A) stretches narrow the DNA minor groove, potentially enhancing electrostatic interactions between the DNA phosphate backbone and the sprocket arginine (Rohs et al 2009;West et al 2010).…”

“…Studies have suggested that sprocket arginine-DNA contacts may play an important role in the rotational positioning of nucleosomes (Luger et al 1997;Harp et al 2000;Rohs et al 2009;Wang et al 2010;West et al 2010). For example, short poly(A) stretches narrow the DNA minor groove, potentially enhancing electrostatic interactions between the DNA phosphate backbone and the sprocket arginine (Rohs et al 2009;West et al 2010).While sprocket arginine residues appear to have unique and important roles in DNA binding and are highly conserved among eukaryotic species, mutational screens in yeast revealed that only one of these arginine residues, H4 R45, is essential for cell viability (Matsubara et al 2007;Dai et al 2008;Nakanishi et al 2008) (Figure 1B Mutations in the H4 R45 residue (H4 R45C and H4 R45H) were originally isolated from a yeast genetic screen for switch-independent (sin) mutants (Kruger et al 1995). Expression of the H4 R45C (or R45H) mutant partially alleviates the requirement for the SWI/SNF remodeling complex to activate the expression of the yeast homothallic switching endonuclease (HO) gene.…”

Twist Neutrality and the Diameter of the Nucleosome Core Particle

“…Electrostatic interactions between DNA and the histones contribute to the stability of the nucleosome [9,10], as well as of any formed superstructures such as the 30 nm filament [11,12,13]. During the last decade, or two, it has become clear that the functional roles of chromatin/nucleosomes/histones are much richer than being limited to that of compaction [14,15,16].…”