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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:p>The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&amp;Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer\u2013promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.<\/jats:p>","DOI":"10.1073\/pnas.2402518121","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T11:35:51Z","timestamp":1725968151000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Three-dimensional chromatin mapping of sensory neurons reveals that promoter\u2013enhancer looping is required for axonal regeneration"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-8090","authenticated-orcid":false,"given":"Ilaria","family":"Palmisano","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"},{"name":"Department of Neuroscience, Department of Plastic and Reconstructive Surgery, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Miami, Coral Gables, FL 33124-4245"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7142-1068","authenticated-orcid":false,"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2889-3288","authenticated-orcid":false,"given":"Matthias","family":"Merkenschlager","sequence":"additional","affiliation":[{"name":"The Institute of Clinical Sciences, Medical Research Council, Laboratory of Medical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2070-7508","authenticated-orcid":false,"given":"Franziska","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7287-7707","authenticated-orcid":false,"given":"Jessica","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Toscano Rivalta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Brain Sciences, Centre for Restorative Neuroscience, Imperial College London, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W. 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