Abstract
Recent technological advances have allowed us to map chromatin conformation and uncover the genome’s spatial organization of the genome inside the nucleus. These experiments have revealed the complexities of genome folding, characterized by the presence of loops and domains at different scales, which can change across development and in different cell types. There is strong evidence for a relationship between the topological properties of chromatin contacts and cellular phenotype. Chromatin can be represented as a network, in which genomic fragments are the nodes and connections represent experimentally observed spatial proximity of two genomically distant regions in a specific cell type or biological condition. With this approach we can consider a variety of chromatin features in association with the 3D structure, investigating how nuclear chromatin organization can be related to gene regulation, replication, malignancy, phenotypic variability and plasticity. We briefly review the results obtained on genome architecture through network theoretic approaches. As previously observed in protein-protein interaction networks and many types of non-biological networks, external conditions could shape network topology through a yet unidentified structure-function relationship. Similar to scientists studying the brain, we are confronted with a duality between a spatially embedded network of physical contacts, a related network of correlation in the dynamics of network nodes and, finally, an abstract definition of function of this network, related to phenotype. We summarise major developments in the study of networks in other fields, which we think can suggest a path towards better understanding how 3D genome configuration can impact biological function and adaptation to the environment.
Highlights
The 4D Nucleome: Features and Dynamics of Chromatin ContactsFor just over 10 years we have had the tools to explore chromosome conformation inside the nucleus with Hi-C (Lieberman-Aiden et al, 2009) and related techniques
Chromatin Network Structure-Function Relationships et al, 2009), HiChIP (Mumbach et al, 2016), micro-C (Hsieh et al, 2015)], alternative approaches provide an independent picture of nuclear organization
Chromatin is the common substrate that unifies these three different biological processes and we have proposed that the chromatin context, including local and global conformation, could be considered as one of the important factors affecting variability in methylation, gene expression and phenotype (Ecker et al, 2018)
Summary
The 4D Nucleome: Features and Dynamics of Chromatin ContactsFor just over 10 years we have had the tools to explore chromosome conformation inside the nucleus with Hi-C (Lieberman-Aiden et al, 2009) and related techniques. Changes in the 3D looping structures of chromatin in neurons following their activation have been shown to affect gene expression on different time scales (Beagan et al, 2020).
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