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The<jats:italic>Tcra\/Tcrd<\/jats:italic>locus recombines<jats:italic>Tcrd<\/jats:italic>gene segments in CD4<jats:sup>\u2212<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup>double-negative thymocytes and<jats:italic>Tcra<\/jats:italic>gene segments in CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>double-positive thymocytes. Initial V<jats:sub>\u03b1<\/jats:sub>-to-J<jats:sub>\u03b1<\/jats:sub>recombination occurs within a chromosomal domain that displays a contracted conformation in both thymocyte subsets. We used chromosome conformation capture to demonstrate that the<jats:italic>Tcra<\/jats:italic>enhancer (E<jats:sub>\u03b1<\/jats:sub>) interacts directly with V<jats:sub>\u03b1<\/jats:sub>and J<jats:sub>\u03b1<\/jats:sub>gene segments distributed across this domain, specifically in double-positive thymocytes. Moreover, E<jats:sub>\u03b1<\/jats:sub>promotes interactions between these V<jats:sub>\u03b1<\/jats:sub>and J<jats:sub>\u03b1<\/jats:sub>segments that should facilitate their synapsis. We found that the CCCTC-binding factor (CTCF) binds to E<jats:sub>\u03b1<\/jats:sub>and to many locus promoters, biases E<jats:sub>\u03b1<\/jats:sub>to interact with these promoters, and is required for efficient V<jats:sub>\u03b1<\/jats:sub>\u2013J<jats:sub>\u03b1<\/jats:sub>recombination. Our data indicate that E<jats:sub>\u03b1<\/jats:sub>and CTCF cooperate to create a developmentally regulated chromatin hub that supports V<jats:sub>\u03b1<\/jats:sub>\u2013J<jats:sub>\u03b1<\/jats:sub>synapsis and recombination.<\/jats:p>","DOI":"10.1073\/pnas.1214131109","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T06:01:27Z","timestamp":1353391287000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":73,"title":["<i>Tcra<\/i>gene recombination is supported by a<i>Tcra<\/i>enhancer- and CTCF-dependent chromatin hub"],"prefix":"10.1073","volume":"109","author":[{"given":"Han-Yu","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Immunology, Duke University Medical Center, Durham, NC 27710;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyoti","family":"Verma-Gaur","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Torkamani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Translational Science Institute, La Jolla, CA 92037; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann J.","family":"Feeney","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Galjart","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus Medical College, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Krangel","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University Medical Center, Durham, NC 27710;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2012,11,19]]},"reference":[{"key":"e_1_1_2_17_8_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2941"},{"key":"e_1_1_2_17_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.07.016"},{"key":"e_1_1_2_17_8_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100772"},{"key":"e_1_1_2_17_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10495"},{"key":"e_1_1_2_17_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.014"},{"key":"e_1_3_4_1_2","first-page":"49","article-title":"Biochemistry of V(D)J recombination","volume":"290","author":"Schatz DG","year":"2005","unstructured":"DG Schatz, E Spanopoulou, Biochemistry of V(D)J recombination. 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