Long Distance Chromatin Interactions

Abstract

The dynamics of chromatin folding has an important role in regulating gene expression in higher eukaryotes. Detailed studies of several model loci, such as beta-globin, have shown that the formation of loops mediated by the interaction between specific regulatory elements that are located hundreds of kilobases away is crucial in gene control. This observation gives rise to an important question: how can a set of widely spaced elements communicate in order to regulate a specific target gene.Recently a computational model has been proposed by Mukhopadhyay et al to explain the formation of long-range chromatin loops. This model is based on attractive nucleosome-nucleosome interaction, allowing the monomers of a chromatin polymer to stick to each other temporarily when in the vicinity of each other. This model shows the enhanced long range contact behavior consistent with shown in recent studies and predicts suppression of pseudoknot formation in chromatin folding. However, it remains to be understood why the chromatin polymer model behaves this way. To answer this question, we propose to look at the structure of the temporarily collapsed configurations of a polymer in certain ranges of lengths and attraction strengths. In particular, our aim is to calculate the crossover scale between the collapsed polymer at longer distance and the folded branched polymer at shorter distance. Such theoretical predictions from a polymer model combined with simulations of polymer conformations (both lattice polymer models and bead-spring models), would tell us whether, in the realistic model, there are certain parameter combinations that has to be fine-tuned to get the suppression of pseudoknots. We hope this study leads to a better understanding of the role of non-specific interactions of the polymer physics of chromatin.