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RUNX1, a well-known transcription factor for T-cell differentiation, has recently been described to act in addition as a recombinase cofactor for TCR\u03b4 gene rearrangements. In this work we employed a RUNX1 knock-out mouse model and demonstrate by deep TCR\u03b2 sequencing, immunostaining and chromatin immunoprecipitation that RUNX1 binds to the initiation site of TCR\u03b2 rearrangement and its homozygous inactivation induces severe structural changes of the rearranged TCR\u03b2 gene, whereas heterozygous inactivation has almost no impact. To compare the mouse model results to the situation in Acute Lymphoblastic Leukemia (ALL) we analyzed TCR\u03b2 gene rearrangements in T-ALL samples harboring heterozygous Runx1 mutations. Comparable to the <jats:italic>Runx1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mouse model, heterozygous Runx1 mutations in T-ALL patients displayed no detectable impact on TCR\u03b2 rearrangements. Furthermore, we reanalyzed published sequence data from recurrent deletion borders of ALL patients carrying an <jats:italic>ETV6-RUNX1<\/jats:italic> translocation. RUNX1 motifs were significantly overrepresented at the deletion ends arguing for a role of RUNX1 in the deletion mechanism. Collectively, our data imply a role of RUNX1 as recombinase cofactor for both physiological and aberrant deletions.<\/jats:p>","DOI":"10.1038\/s41598-020-65744-0","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T10:03:36Z","timestamp":1592820216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evidence for a role of RUNX1 as recombinase cofactor for TCR\u03b2 rearrangements and pathological deletions in ETV6-RUNX1 ALL"],"prefix":"10.1038","volume":"10","author":[{"given":"V.","family":"Seitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Kleo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dr\u00f6ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Schaper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Elezkurtaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Bedjaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Dimitrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Sommerfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"von der Wall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lenze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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