Computational Elucidation of self-organization of E. coli chromosome underlying HI-C data

Abstract

The chromosome of Escherichia Coli (E. coli) is riddled with multi-faceted complexity and its nature of organization is slowly getting recognised. The emergence of chromosome conformation capture techniques and super-resolution microscopy are providing newer ways to explore chromosome organization, and dynamics and its effect on gene expression. Here we combine a beads-on-a-spring polymer-based framework with recently reported high-resolution Hi-C data of E. coli chromosome to develop a comprehensive model of E. coli chromosome at 5 kilo base-pair resolution. The model captures a self-organised chromosome composed of linearly organised genetic loci, and segregated macrodomains within a ring-like helicoid architecture, with no net chirality. Additionally, a genome-wide map identifies multiple chromosomal interaction domains (CIDs) and corroborates well with a transcription-centric model of the E. coli chromosome. The investigation further demonstrates that while only a small fraction of the Hi-C contacts is dictating the underlying chromosomal organization, a random-walk polymer chain devoid of Hi-C encoded contact information would fail to map the key genomic interactions unique to E. coli. Collectively, the present work, integrated with Hi-C interaction, elucidates the organization of bacterial chromosome at multiple scales, ranging from identifying a helical, macro-domain-segregated morphology at coarse-grained scale to a manifestation of CIDs at a fine-grained scale.