{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:56Z","timestamp":1785405596632,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,16]]},"group-title":"Biophysics","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["929737"],"award-info":[{"award-number":["929737"]}],"id":[{"id":"https:\/\/ror.org\/01cmst727","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2232049"],"award-info":[{"award-number":["2232049"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI082850"],"award-info":[{"award-number":["R01 AI082850"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R21 AI193549"],"award-info":[{"award-number":["1R21 AI193549"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Antibody diversity is generated through stochastic rearrangement of the immunoglobulin heavy chain locus (Igh) involving the recombination of variable (V\n                  <jats:sub>H<\/jats:sub>\n                  ), diversity (D\n                  <jats:sub>H<\/jats:sub>\n                  ) and joining (J\n                  <jats:sub>H<\/jats:sub>\n                  ) gene segments. How coding elements within the Igh locus locate one another in the complex nuclear environment is not understood. Here, we sought to identify the molecular mechanisms and physical principles that govern V\n                  <jats:sub>H-<\/jats:sub>\n                  D\n                  <jats:sub>H<\/jats:sub>\n                  J\n                  <jats:sub>H<\/jats:sub>\n                  genomic encounters. We found that transcription imposed a local confinement that stabilized interactions between spatially proximal genomic elements. The loop anchor CTCF modestly constrained population-average chromatin motion, whereas cohesin-mediated loops established large-scale confinement and reinforced self-similarity of V\n                  <jats:sub>H-<\/jats:sub>\n                  D\n                  <jats:sub>H<\/jats:sub>\n                  J\n                  <jats:sub>H<\/jats:sub>\n                  motion across spatial and temporal scales. Quantitative scaling arguments for first-passage times revealed that encounter frequencies between remote V\n                  <jats:sub>H-<\/jats:sub>\n                  D\n                  <jats:sub>H<\/jats:sub>\n                  J\n                  <jats:sub>H<\/jats:sub>\n                  genomic regions are governed by the interplay of diffusivity and spatial proximity. Together, these findings show that the hierarchy of confinements imposed by transcription and loop extrusion provides the balance between stability and mobility required to regulate genomic encounter frequencies.\n                <\/jats:p>","DOI":"10.64898\/2026.07.12.738087","type":"posted-content","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:00:26Z","timestamp":1784214026000},"source":"Crossref","is-referenced-by-count":0,"title":["A hierarchy of spatial confinements governs chromatin dynamics and genomic encounters"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5448-2960","authenticated-orcid":false,"given":"Megan","family":"Aubrey","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Prusy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-8538","authenticated-orcid":false,"given":"Olga K.","family":"Dudko","sequence":"additional","affiliation":[{"name":"Department of Physics, University of California, San Diego La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-507X","authenticated-orcid":false,"given":"Cornelis","family":"Murre","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072005550898000_2026.07.12.738087v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1978.042.01.035"},{"key":"2026072005550898000_2026.07.12.738087v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030157"},{"key":"2026072005550898000_2026.07.12.738087v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181369"},{"key":"2026072005550898000_2026.07.12.738087v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature11082"},{"key":"2026072005550898000_2026.07.12.738087v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"2026072005550898000_2026.07.12.738087v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.04.008"},{"key":"2026072005550898000_2026.07.12.738087v1.7","doi-asserted-by":"crossref","unstructured":"Sanborn, A.L. , Rao, S.S.P. , Huang, S.-C. , Durand, N.C. , Huntley, M.H. , Jewett, A.I. , Bochkov, I.D. , Chinnappan, D. , Cutkosky, A. , Li, J. , et al. 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