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Regulatory T cells (Treg) are mainly generated in the thymus as a subpopulation of T cells specializing in suppressing excessive immune responses. Here, by comprehensively mapping 3D chromatin organization during Treg cell differentiation, we show that Treg-specific chromatin structures were progressively established during its lineage specification, and highly associated with Treg signature gene expression. Additionally, the binding sites of Foxp3, a Treg lineage specifying transcription factor, were highly enriched at Treg-specific chromatin loop anchors. Further comparison of the chromatin interactions between wide-type Tregs versus Treg cells from Foxp3 knock-in\/knockout or newly-generated Foxp3 domain-swap mutant mouse revealed that Foxp3 was essential for the establishment of Treg-specific 3D chromatin architecture, although it was not dependent on the formation of the Foxp3 domain-swapped dimer. These results highlighted an underappreciated role of Foxp3 in modulating Treg-specific 3D chromatin structure formation.<\/jats:p>","DOI":"10.1101\/2023.02.22.529589","type":"posted-content","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T16:21:23Z","timestamp":1677169283000},"source":"Crossref","is-referenced-by-count":5,"title":["Foxp3 Orchestrates Reorganization of Chromatin Architecture to Establish Regulatory T Cell 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