biostudies-literatureRamirez RNNIAID NIH HHSNIGMS NIH HHSeabj9836https://www.ebi.ac.uk/biostudies/studies/S-EPMC9059705biostudies-literatureUnknown7(67)Gene expression programs are specified by higher-order chromatin structure and enhancer-promoter loops (EPLs). T regulatory cell (T_reg) identity is dominantly specified by the transcription factor (TF) FoxP3, whose mechanism of action is unclear. We applied chromatin conformation capture with immunoprecipitation (HiChIP) in T_reg and closely related conventional CD4⁺ T cells (T_conv). EPLs identified by H3K27Ac HiChIP showed a range of connection intensity, with some superconnected genes. TF-specific HiChIP showed that FoxP3 interacts with EPLs at a large number of genes, including some not differentially expressed in T_reg versus T_conv, but enriched at the core T_reg signature loci that it up-regulates. FoxP3 associaScience immunologyFoxP3 associates with enhancer-promoter loops to regulate T_reg-specific gene expression.PMC9059705T32 GM007753R01 AI116834R01 AI150686Leon JRamirez RNMathis DBenoist CChowdhary KfalseFoxP3 associates with enhancer-promoter loops to regulate T_reg-specific gene expression.Gene expression programs are specified by higher-order chromatin structure and enhancer-promoter loops (EPLs). T regulatory cell (T_reg) identity is dominantly specified by the transcription factor (TF) FoxP3, whose mechanism of action is unclear. We applied chromatin conformation capture with immunoprecipitation (HiChIP) in T_reg and closely related conventional CD4⁺ T cells (T_conv). EPLs identified by H3K27Ac HiChIP showed a range of connection intensity, with some superconnected genes. TF-specific HiChIP showed that FoxP3 interacts with EPLs at a large number of genes, including some not differentially expressed in T_reg versus T_conv, but enriched at the core T_reg signature loci that it up-regulates. FoxP3 associa2022-01-01T00:00:00Z2022 Jan2025-04-04T20:35:32.413Z2025-04-04T20:35:32.413ZS-EPMC90597053503003510.1126/sciimmunol.abj9836