title: Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays.
abstract: Heterochromatin protein 1 (HP1) participates in establishing and maintaining heterochromatin via its histone-modification-dependent chromatin interactions. In recent papers HP1 binding to nucleosomal arrays was measured in vitro and interpreted in terms of nearest-neighbour cooperative binding. This mode of chromatin interaction could lead to the spreading of HP1 along the nucleosome chain. Here, we reanalysed previous data by representing the nucleosome chain as a 1D binding lattice and showed how the experimental HP1 binding isotherms can be explained by a simpler model without cooperative interactions between neighboring HP1 dimers. Based on these calculations and spatial models of dinucleosomes and nucleosome chains, we propose that binding stoichiometry depends on the nucleosome repeat length (NRL) rather than protein interactions between HP1 dimers. According to our calculations, more open nucleosome arrays with long DNA linkers are characterized by a larger number of binding sites in comparison to chains with a short NRL. Furthermore, we demonstrate by Monte Carlo simulations that the NRL dependent folding of the nucleosome chain can induce allosteric changes of HP1 binding sites. Thus, HP1 chromatin interactions can be modulated by the change of binding stoichiometry and the type of binding to condensed (methylated) and non-condensed (unmethylated) nucleosome arrays in the absence of direct interactions between HP1 dimers.
authors.affiliation: Deutsches Krebsforschungszentrum & BioQuant, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Teif
authors.forename: Nick
authors.initials: N
authors.lastname: Kepper
authors.forename: Klaus
authors.initials: K
authors.lastname: Yserentant
authors.forename: Gero
authors.initials: G
authors.lastname: Wedemann
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D001665:Binding Sites; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; D000090266:Chromobox Protein Homolog 5; D004247:DNA