Disentangling polymer confinement from specific-folding interactions reveals the drivers of Escherichia coli chromosome organization
- 1Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago , Chicago, IL 60607 ,
- 2Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University , Baltimore, MD 21205 ,
- 3Department of Cell Biology, School of Medicine, Johns Hopkins University , Baltimore, MD 21205 ,
Abstract
The three-dimensional organization of the bacterial chromosome is critical for gene regulation. Chromosome conformation capture (Hi-C) has enabled genome-wide mapping of chromosomal folding, yet ensemble-averaged contact maps entangle biologically specific-folding interactions (SFIs) with nonspecific polymer compaction and mask single-cell heterogeneity. Here, we developed a polymer-based simulation framework in Escherichia coli to address these limitations. We found that a null model of 300 000 random polymer configurations recapitulated the global chromosomal organization observed in Hi-C data, establishing that most Hi-C signals reflect generic polymer behavior in a confined volume. Contrasting null-model predictions with experimental Hi-C data isolated a small subset of SFIs (<7%) and generated a specific-fold ensemble of 20 000 single-cell conformations that reproduced chromosomal interaction domains and single-cell heterogeneity. SFIs were enriched in the ter region, reduced nucleoid accessibility, colocalized with cryptic prophages, and depleted in positively supercoiled regions. H-NS and MatP emerged as major chromosome-wide and local determinants of SFIs, respectively. Furthermore, high-SFI regions correlated with stress-adaptive genes, whereas low-SFI regions harbored housekeeping genes. Together, our results established that a small number of biologically encoded SFIs superimposed on a polymer background shape the E. coli chromosome and gene expression, providing a quantitative framework for dissecting chromosome architecture and function.
Related
- Cell-sized droplet interfaces reorganize protein secondary structures through confinement-enhanced membrane interactions
- Molecular architecture of TE-seeded chromosome-naive initiation networks of protein-protein interactions delineates the Human Protein Map of the assembly of multiprotein complexes
- Bacteroides–Escherichia interactions contribute to colonization resistance against Clostridioides difficile
- Looking Beyond KD for Aptamer Validation: Disentangling Specific Aptamer Binding from Electrostatic Association for Basic Protein Targets
- TDP-43 regulates mitochondrial dsRNA accumulation and chromosome territory formation during prophase I of Drosophila male meiosis
BibTeX
@article{delafrouz2026disentangling,
title = {{Disentangling polymer confinement from specific-folding interactions reveals the drivers of Escherichia coli chromosome organization}},
author = {Pourya Delafrouz and Tanya Nesterova and Frances E Harris and Hammad Farooq and Lin Du and Jian Liu and Ao Ma and Jie Xiao and Jie Liang},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag979},
url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag979/8971829},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Disentangling polymer confinement from specific-folding interactions reveals the drivers of Escherichia coli chromosome organization
AU - Pourya Delafrouz
AU - Tanya Nesterova
AU - Frances E Harris
AU - Hammad Farooq
AU - Lin Du
AU - Jian Liu
AU - Ao Ma
AU - Jie Xiao
AU - Jie Liang
PY - 2026
DA - 2026/10/01
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag979
UR - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag979/8971829
AB - The three-dimensional organization of the bacterial chromosome is critical for gene regulation. Chromosome conformation capture (Hi-C) has enabled genome-wide mapping of chromosomal folding, yet ensemble-averaged contact maps entangle biologically specific-folding interactions (SFIs) with nonspecific polymer compaction and mask single-cell heterogeneity. Here, we developed a polymer-based simulation framework in Escherichia coli to address these limitations. We found that a null model of 300 000 random polymer configurations recapitulated the global chromosomal organization observed in Hi-C data, establishing that most Hi-C signals reflect generic polymer behavior in a confined volume. Contrasting null-model predictions with experimental Hi-C data isolated a small subset of SFIs (<7%) and generated a specific-fold ensemble of 20 000 single-cell conformations that reproduced chromosomal interaction domains and single-cell heterogeneity. SFIs were enriched in the ter region, reduced nucleoid accessibility, colocalized with cryptic prophages, and depleted in positively supercoiled regions. H-NS and MatP emerged as major chromosome-wide and local determinants of SFIs, respectively. Furthermore, high-SFI regions correlated with stress-adaptive genes, whereas low-SFI regions harbored housekeeping genes. Together, our results established that a small number of biologically encoded SFIs superimposed on a polymer background shape the E. coli chromosome and gene expression, providing a quantitative framework for dissecting chromosome architecture and function.
SN - 0305-1048
SN - 1362-4962
ER -