title: Nonspecific bridging-induced attraction drives clustering of DNA-binding proteins and genome organization.
abstract: Molecular dynamics simulations are used to model proteins that diffuse to DNA, bind, and dissociate; in the absence of any explicit interaction between proteins, or between templates, binding spontaneously induces local DNA compaction and protein aggregation. Small bivalent proteins form into rows [as on binding of the bacterial histone-like nucleoid-structuring protein (H-NS)], large proteins into quasi-spherical aggregates (as on nanoparticle binding), and cylinders with eight binding sites (representing octameric nucleosomal cores) into irregularly folded clusters (like those seen in nucleosomal strings). Binding of RNA polymerase II and a transcription factor (NFκB) to the appropriate sites on four human chromosomes generates protein clusters analogous to transcription factories, multiscale loops, and intrachromosomal contacts that mimic those found in vivo. We suggest that this emergent behavior of clustering is driven by an entropic bridging-induced attraction that minimizes bending and looping penalties in the template.
authors.affiliation: Scottish Universities Physics Alliance (SUPA), School of Physics, University of Edinburgh, Edinburgh EH9 3JZ, United Kingdom.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Brackley
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Argyris
authors.initials: A
authors.lastname: Papantonis
authors.forename: Peter R
authors.initials: PR
authors.lastname: Cook
authors.forename: Davide
authors.initials: D
authors.lastname: Marenduzzo
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D002877:Chromosomes, Human / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D016328:NF-kappa B; D004247:DNA; D012319:RNA Polymerase II
keywords: Brownian dynamics; chromatin looping; nucleosome; polymer physics