{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:43:25Z","timestamp":1781106205946,"version":"3.54.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,10,26]]},"abstract":"<jats:p>\n                    To study\n                    <jats:italic>RAG2<\/jats:italic>\n                    gene regulation\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we developed a blastocyst complementation method in which\n                    <jats:italic>RAG2<\/jats:italic>\n                    -deficient embryonic stem cells were transfected with genomic clones containing\n                    <jats:italic>RAG2<\/jats:italic>\n                    and then assessed for their ability to generate lymphocytes. A\n                    <jats:italic>RAG2<\/jats:italic>\n                    genomic clone that contained only the\n                    <jats:italic>RAG2<\/jats:italic>\n                    promoter sequences rescued V(D)J recombination in\n                    <jats:italic>RAG2<\/jats:italic>\n                    -deficient pro-B cell lines, but did not rescue development of\n                    <jats:italic>RAG2<\/jats:italic>\n                    -deficient lymphocytes\n                    <jats:italic>in vivo<\/jats:italic>\n                    . However, inclusion of varying lengths of sequences 5\u2032 of the\n                    <jats:italic>RAG2<\/jats:italic>\n                    promoter generated constructs capable of rescuing only\n                    <jats:italic>in vivo<\/jats:italic>\n                    B cell development, as well as other constructs that rescued both B and T cell development. In particular, the 2-kb 5\u2032 region starting just upstream of the RAG2 promoter, as well as the region from 2\u20137 kb 5\u2032, could independently drive B cell development, but not efficient T cell development. Deletion of the 2-kb 5\u2032 region from the murine germ line demonstrated that this region was not required for\n                    <jats:italic>RAG<\/jats:italic>\n                    expression sufficient to generate normal B or T cell numbers, implying redundancy among 5\u2032 elements. We conclude that\n                    <jats:italic>RAG2<\/jats:italic>\n                    expression\n                    <jats:italic>in vivo<\/jats:italic>\n                    requires elements beyond the core promoter, that such elements contribute to differential regulation in the B vs. T lineages, and that sequences sufficient to direct B cell expression are located in the promoter-proximal 5\u2032 region.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.22.12713","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"12713-12718","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["<i>RAG2<\/i>\n                    is regulated differentially in B and T cells by elements 5\u2032 of the promoter"],"prefix":"10.1073","volume":"96","author":[{"given":"Robert J.","family":"Monroe","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, The Children\u2019s Hospital, Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Children\u2019s Hospital, Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Ferrini","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Children\u2019s Hospital, Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Davidson","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Children\u2019s Hospital, Center for Blood Research and Department of Genetics, 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