Chromatin assortativity: Integrating epigenomic data and 3D genomic structure
Year: 2015
Type: preprint
Abstract: Background The field of 3D chromatin interaction mapping is changing our point of view on the genome, paving the way for new insights into its organization. Network analysis is a natural and powerful way of modelling chromatin interactions. Assortativity is a network property that has allowed social scientists to identify factors that affect how people establish social ties. We propose a new approach, using chromatin assortativity to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts in the nucleus. Results We use high-resolution Promoter Capture Hi-C and Hi-Cap data as well as ChIA-PET data from mouse embryonic stem cells to investigate promoter-centered chromatin interaction networks. We then calculate the presence of a collection of 78 epigenomic features in the chromatin fragments constituting the nodes of the network. We use the chromatin assortativity approach to estimate the association of these epigenomic features to the 2 topology of four different chromatin interaction networks and use high assortativity to identify features localized in specific and connected areas of the network. We found Polycomb Group proteins and associated histone marks as the features with the highest chromatin assortativity in promoter-centred networks. We then ask which features distinguish contacts amongst promoters from contacts between promoters and other genomic elements. Remarkably, we observe higher chromatin assortativity of the actively elongating form of RNA Polymerase 2 (RNAPII) compared to inactive forms only in interactions between promoters and other elements. This suggests a prominent role for active elongation in distal regulatory interactions. Conclusions Contacts amongst promoters and between promoters and other elements have different characteristic epigenomic features. Using chromatin assortativity we identify a possible role for the elongating form of RNAPII in mediating interactions among promoters, enhancers and transcribed gene bodies. Our approach facilitates the study of multiple genome-wide epigenomic profiles, considering network topology and allowing for the comparison of any number of chromatin interaction networks.
Source: arXiv (Cornell University)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2731111365