{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:45Z","timestamp":1791561045078,"version":"4.3.4"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,7,3]]},"abstract":"<jats:p>\n                    Human Burkitt lymphomas are divided into two main clinical variants: the\n                    <jats:italic>endemic<\/jats:italic>\n                    form, affecting African children infected with malaria and the Epstein-Barr virus, and the\n                    <jats:italic>sporadic<\/jats:italic>\n                    form, distributed across the rest of the world. However, whereas\n                    <jats:italic>sporadic<\/jats:italic>\n                    translocations decapitate\n                    <jats:italic>Myc<\/jats:italic>\n                    from 5\u2032 proximal regulatory elements, most endemic events occur hundreds of kilobases away from\n                    <jats:italic>Myc<\/jats:italic>\n                    . The origin of these rearrangements and how they deregulate oncogenes at such distances remain unclear. We here recapitulate endemic Burkitt lymphoma-like translocations in plasmacytomas from uracil\n                    <jats:italic>N<\/jats:italic>\n                    -glycosylase and activation-induced cytidine deaminase-deficient mice. Mapping of translocation breakpoints using an acetylated histone H3 lysine 9 chromatin immunoprecipitation sequencing approach reveals\n                    <jats:italic>Igh<\/jats:italic>\n                    fusions up to \u223c350 kb upstream of\n                    <jats:italic>Myc<\/jats:italic>\n                    or the related oncogene\n                    <jats:italic>Mycn<\/jats:italic>\n                    . A comprehensive analysis of epigenetic marks, PolII recruitment, and transcription in tumor cells demonstrates that the 3\u2032\n                    <jats:italic>Igh<\/jats:italic>\n                    enhancer (E\u03b1) vastly remodels \u223c450 kb of chromatin into translocated sequences, leading to significant polymerase occupancy and constitutive oncogene expression. We show that this long-range epigenetic reprogramming is directly proportional to the physical interaction of E\u03b1 with translocated sites. Our studies thus uncover the extent of epigenetic remodeling by\n                    <jats:italic>Ig<\/jats:italic>\n                    3\u2032 enhancers and provide a rationale for the long-range deregulation of translocated oncogenes in endemic Burkitt lymphomas. The data also shed light on the origin of endemic-like chromosomal rearrangements.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1200106109","type":"journal-article","created":{"date-parts":[[2012,6,18]],"date-time":"2012-06-18T23:15:14Z","timestamp":1340061314000},"page":"10972-10977","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":27,"title":["Mouse model of endemic Burkitt translocations reveals the long-range boundaries of\n                    <i>Ig<\/i>\n                    -mediated oncogene deregulation"],"prefix":"10.1073","volume":"109","author":[{"given":"Alexander L.","family":"Kovalchuk","sequence":"first","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Ansarah-Sobrinho","sequence":"additional","affiliation":[{"name":"Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofir","family":"Hakim","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Resch","sequence":"additional","affiliation":[{"name":"Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Tolarov\u00e1","sequence":"additional","affiliation":[{"name":"Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Dubois","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arito","family":"Yamane","sequence":"additional","affiliation":[{"name":"Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Klein","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon L.","family":"Hager","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Herbert C.","family":"Morse","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Potter","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel C.","family":"Nussenzweig","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, and"},{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; 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