Chromatin interaction networks and higher order architectures of eukaryotic genomes

Abstract

Eukaryotic genome is, not only linearly but also spatially, organized into non-random architecture. Though the linear organization of genes and their epigenetic descriptors are well characterized, the relevance of their spatial organization is beginning to unfold only recently. It is increasingly being recognized that physical interactions among distant genomic elements could serve as an important mean to eukaryotic genome regulation. With the advent of proximity ligation based techniques coupled with next generation sequencing, it is now possible to explore whole genome chromatin interactions at high resolution. Emerging data on genome-wide chromatin interactions suggest that distantly located genes are not independent entities and instead cross-talk with each other in an extensive manner, supporting the notion of “chromatin interaction networks”. Moreover, the data also advance the field to “3-dimensional (3D) chromatin structure and dynamics”, which would enable molecular biologists to explore the spatiotemporal regulation of genome. In this article, we introduce a stepwise topological transformation of genome from 1-dimension (1D, linear) to 2-dimension (2D, networks) to 3-dimension (3D, architecture) and discuss how such transformations could advance our understanding of genome biology.

Large-Scale Functional Organization of Long-Range Chromatin Interaction Networks

“…The nonrandom topological properties of most real-world networks are strongly associated with their robustness and functional organization ( Albert et al, 2000 ; Barabási and Albert, 1999 ; Barabási and Oltvai, 2004 ), which has motivated molecular biologists to explore cellular regulation using a systems approach. Although most cellular networks, such as gene-regulatory, metabolic, protein-protein interaction, and signaling networks, are being widely studied, the extensive communications among regulatory elements in the genome have not been viewed in a complex-network context ( Singh Sandhu et al, 2011 ).…”

Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing technology and application

“…Anchors in different interacting pairs are not isolated - they may overlap with or link to other counterparts in different physical regions. This leads to the concept of "chromatin interaction networks" [ 31 ], which refers to the 2D structure of genome-wide chromatin interaction (Figure 5 ). Like many cellular networks, chromatin interaction network [ 20 ] has scale-free and modular topology - most nodes participate in only one or two interactions, while a few nodes, known as "hubs", connect with a disproportionately high number of nodes.…”

“… Transformation from current chromatin interactions to future 3D/4D dynamics . This figure is from Sandhu et al, 2011 [ 31 ]. …”

“…In future studies, we can not only apply the method to other specific kinds of genes, but also combine interdependent networks, since cellular activities happen together and link to each other. Also, chromatin interaction networks may lay the foundation of 3D or even 4D genome waves, which transfer from static to dynamic [ 31 ].…”

QuIN: A Web Server for Querying and Visualizing Chromatin Interaction Networks

“…A commonly used tool for this is the UCSC Genome Browser [ 6 ]. However, two and three dimensional representations of chromatin interactions in the form of networks and three-dimensional models can provide a global view of the interactions and facilitate the use of established network analysis methods and measures on these datasets [ 7 ]. For example, network representation of RNA Pol2 ChIA-PET data revealed that loci harboring disease-associated SNPs are differently connected in chromatin interaction networks [ 8 ].…”