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Yet, over half of the TAL1\n                    <jats:sup>+<\/jats:sup>\n                    cases lack\n                    <jats:italic>TAL1<\/jats:italic>\n                    lesions, suggesting unrecognized (epi)genetic deregulation mechanisms. Here we show that\n                    <jats:italic>TAL1<\/jats:italic>\n                    is normally silenced in the T-cell lineage, and that the polycomb H3K27me3-repressive mark is focally diminished in TAL1\n                    <jats:sup>+<\/jats:sup>\n                    T-ALLs. Sequencing reveals that &gt;20% of monoallelic TAL1\n                    <jats:sup>+<\/jats:sup>\n                    patients without previously known alterations display microinsertions or RAG1\/2-mediated episomal reintegration in a single site 5\u2032 to\n                    <jats:italic>TAL1<\/jats:italic>\n                    . Using \u2018allelic-ChIP\u2019 and CrispR assays, we demonstrate that such insertions induce a selective switch from H3K27me3 to H3K27ac at the inserted but not the germline allele. We also show that, despite a considerable mechanistic diversity, the mode of oncogenic\n                    <jats:italic>TAL1<\/jats:italic>\n                    activation, rather than expression levels, impact on clinical outcome. Altogether, these studies establish site-specific epigenetic desilencing as a mechanism of oncogenic activation.\n                  <\/jats:p>","DOI":"10.1038\/ncomms7094","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T08:40:25Z","timestamp":1422002425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Site- and allele-specific polycomb dysregulation in T-cell leukaemia"],"prefix":"10.1038","volume":"6","author":[{"given":"Jean-Marc","family":"Navarro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Touzart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie C.","family":"Pradel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Loosveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Koubi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Fenouil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Le Noir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ahmad","family":"Maqbool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Morgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Gregoire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Jaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Mamessier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Pignon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"Hacein-Bey-Abina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo G.","family":"Gut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Dombret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Macintyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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