{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:36:50Z","timestamp":1792690610415,"version":"4.5.0"},"posted":{"date-parts":[[2026,5,23]]},"group-title":"Genomics","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:italic>E. coli<\/jats:italic>\n                  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 (&lt; 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\n                  <jats:italic>ter<\/jats:italic>\n                  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\n                  <jats:italic>E. coli<\/jats:italic>\n                  chromosome and gene expression, providing a quantitative framework for dissecting chromosome architecture and function.\n                <\/jats:p>","DOI":"10.64898\/2026.05.20.726692","type":"posted-content","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T19:10:14Z","timestamp":1779563414000},"source":"Crossref","is-referenced-by-count":1,"title":["Disentangling polymer confinement from specific-folding interactions reveals the drivers of\n                  <i>E. coli<\/i>\n                  chromosome organization"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8665-1020","authenticated-orcid":false,"given":"Pourya","family":"Delafrouz","sequence":"first","affiliation":[{"name":"Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Nesterova","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-298X","authenticated-orcid":false,"given":"Hammad","family":"Farooq","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8986-9812","authenticated-orcid":false,"given":"Lin","family":"Du","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-0349","authenticated-orcid":false,"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-5437","authenticated-orcid":false,"given":"Jie","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-6427","authenticated-orcid":false,"given":"Jie","family":"Liang","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics and Quantitative Biology, Richard and Loan Hill Department of Biomedical Engineering, The University of Illinois Chicago, Chicago, IL, 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