Generating Chromosome Geometries in a Minimal Cell From Cryo-Electron Tomograms and Chromosome Conformation Capture Maps
Year: 2021
Type: article
Abstract: 's, and the corresponding reduction in complexity and scale provides a unique opportunity for whole-cell modeling. Previous work established genome-scale gene essentiality and proteomics data along with its essential metabolic network and a kinetic model of genetic information processing. In addition to that information, whole-cell, spatially-resolved kinetic models require cellular architecture, including spatial distributions of ribosomes and the circular chromosome's configuration. We reconstruct cellular architectures of Syn3A cells at the single-cell level directly from cryo-electron tomograms, including the ribosome distributions. We present a method of generating self-avoiding circular chromosome configurations in a lattice model with a resolution of 11.8 bp per monomer on a 4 nm cubic lattice. Realizations of the chromosome configurations are constrained by the ribosomes and geometry reconstructed from the tomograms and include DNA loops suggested by experimental chromosome conformation capture (3C) maps. Using ensembles of simulated chromosome configurations we predict chromosome contact maps for Syn3A cells at resolutions of 250 bp and greater and compare them to the experimental maps. Additionally, the spatial distributions of ribosomes and the DNA-crowding resulting from the individual chromosome configurations can be used to identify macromolecular structures formed from ribosomes and DNA, such as polysomes and expressomes.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: National Science Foundation, Agouron Institute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, University of Illinois at Urbana-Champaign, University of California, San Diego, University of California, San Francisco, National Institute of General Medical Sciences, Division of Molecular and Cellular Biosciences, Division of Biological Infrastructure
Awards: G1274366514, Cell and Molecular Genetics Training Program, G3372464033, Resource for Biocomputing Visualization and Informatics, Center for Macromolecular Modeling and Bioinformatics, G3815949496, G4170261888, Opening Windows into the Cell: Revealing the Molecular Architecture of the Nuclear Periphery, G4815039349, G5528850602, MRI: Acquisition of Aquilos Dual-Beam Microscope, RoL:FELS:RAISE: Building and Modeling Synthetic Bacterial Cells, Dynamic bacterial chromatin organization: unraveling the code translating environmental cues to transcriptional changes, Collaborative Research: PoLS Student Research Network, PFC: Center for the Physics of Living Cells, Netherlands X-omics Initiative, RoL: FELS: RAISE: Balancing demands of Minimal Cell, Simulating a minimal cell: Integrating experiment and theory, Resolving the fundamental building principles of the genome, G9000013378, G9000133700, Molecular and cellular mechanisms of circadian timekeeping in a prokaryote model
OpenAlex ID: W3185854339