Role of nucleosome positioning in 3D chromatin organization and loop formation
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Role of nucleosome positioning in 3D chromatin organization and loop formation HUNGYO KHARERIN, PAIKE J BHAT and RANJITH PADINHATEERI* Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India *Corresponding author (Email, [email protected])
We present a physics-based polymer model that can investigate 3D organization of chromatin accounting for DNA elasticity, DNA-bending due to nucleosomes, and 1D organization of nucleosomes along DNA. We find that the packing density of chromatin oscillates between densities corresponding to highly folded and extended configurations as we change the nucleosome organization (length of linker DNA). We compute the looping probability of chromatin and show that the presence of nucleosomes increases the looping probability of the chain compared to that of a bare DNA. We also show that looping probability has a large variability depending on the nature of nucleosome organization and density of linker histones. Keywords.
3D chromatin; J-factor; linker DNA; nucleosome positioning; polymer model
1. Introduction Chromatin is a long polymer made of a string of nucleosomes –DNA-histone complexes –that can be further folded into a hierarchy of compacted structures. Some of the highly compacted regions of chromatin are inaccessible to other proteins/ enzymes and hence genes in that regions cannot be transcribed – such regions are known as heterochromatin (Huisinga et al. 2006; Wang et al. 2016). Regions of chromatin that are in the decondensed state – known as euchromatin – resemble an extended fiber like a string made of many beads (Dekker 2008a). At this level of packing hierarchy, the chromatin is thought to be transcriptionally active. While some set of genes are either transcriptionally active or repressed all the time, some other set of genes may need to switch between transcriptionally active and repressed states. In this process of gene regulation, chromatin needs to be folded, often into loops, and sometimes into highly packed states.
This article is part of the Topical Collection: Chromatin Biology and Epigenetics.
Recent ‘chromatin conformation capture’ experiments (e.g., 3C and Hi-C) have provided us a lot of information about the organization of chromatin in cells. The experiments provide contact probabilities of genomic sites that lie kilobase pair (kbp) to megabase pair (mbp) apart (Dekker et al. 2002; Lieberman-Aiden et al. 2009; Hsieh et al. 2015). These data have revealed that chromatin is composed of organizing modules such as topologically associated domains (TADs) and chromatin loops (Nora et al. 2012). In the length scale of a mbp, the interaction frequency as a function of genomic distance has been found to show a power-law behavior. Polymer theory has been used to understand the 3D organization of the chromatin in the nucleus and also to explain the scaling behavior of the polymer with respect to its size (Le et al. 2013; Haddad et al. 2
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