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.

The physics of epigenetics

“…However the spreading of HP1 along an H3K9me3 epigenetic domain is still a matter of debate. Thus in the latest special issue of JPCM (Everaers and Schiessel, 2015), devoted to the physics of chromatin, two contrasted models have been proposed: the group of Andrew Spakowitz (Mulligan et al, 2015) claims that bridging interaction between HP1 dimers is critical for HP1 spreading, at odds with the group of Karsten Rippe (Teif et al, 2015) who claims that the binding of one HP1 dimer can stabilize a stacked nucleosome conformation and facilitate the binding of a second dimer via an allosteric change of the nucleosome substrate, with no need for a direct interaction between neighboring HP1 dimers. It is to be noted that both groups could reproduce the in vitro binding curves of the yeast analog of HP1 (Swi6) on mono-and dinucleosomes as well as on arrays of nucleosomes.…”

Changing Chromatin Fiber Conformation by Nucleosome Repositioning

“…For regions with irregular spaced nucleosomes only the direct interacting nucleosomes might be affected. Nevertheless, also in this case long-range interactions might be induced by a subsequent change of nucleosome stacking interactions and/or the redistribution of chromosomal proteins that could bind to a stacked dinucleosome as proposed for heterochomatin protein 1 (HP1) (80).…”

Genome maintenance in the context of 4D chromatin condensation

“…Histone methyltransferase SUV39H1 trimethylates the lysine residue 9 of histone H3; this recruits HP1 and establishes constitutive heterochromatin at pericentromeric and telomeric sites [96,97]. Interestingly, the CD and CSD can coordinate to induce an oligomerization process, leading to heterochromatin spreading [98–100]. In S. pombe , Swi6 acts as a transcriptional repressor and its repressive function is vital for sister chromatid cohesion, telomere maintenance and DNA repair [101].…”