Single-molecule imaging of DNA curtains reveals intrinsic energy landscapes for nucleosome deposition.
Here we use single-molecule imaging to determine coarse-grained intrinsic energy landscapes for nucleosome deposition on model DNA substrates. Our results reveal distributions that are correlated with recent in silico predictions, reinforcing the hypothesis that DNA contains some intrinsic positioning information. We also show that cis-regulatory sequences in human DNA coincide with peaks in the intrinsic landscape, whereas valleys correspond to nonregulatory regions, and we present evidence arguing that nucleosome deposition in vertebrates is influenced by factors that are not accounted for by current theory. Finally, we demonstrate that intrinsic landscapes of nucleosomes containing the centromere-specific variant CenH3 are correlated with patterns observed for canonical nucleosomes, arguing that CenH3 does not alter sequence preferences of centromeric nucleosomes. However, the nonhistone protein Scm3 alters the intrinsic landscape of CenH3-containing nucleosomes, enabling them to overcome the otherwise exclusionary effects of poly(dA-dT) tracts, which are enriched in centromeric DNA.
Visnapuu
Mari-Liis
ML
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
Greene
Eric C
EC
D010582:Bacteriophage lambda / Q000737:chemistry; D002503:Centromere / Q000648:ultrastructure; D002843:Chromatin / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D004247:DNA / Q000737:chemistry*; D005821:Genetic Techniques; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D009707:Nucleosomes / Q000378:metabolism*; D045663:Quantum Dots; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D055544:beta-Globins / Q000737:chemistry
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D008051:Lipid Bilayers; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C521684:Scm3 protein, S cerevisiae; D055544:beta-Globins; D004247:DNA