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We investigated the role of these mechanisms at the\n                    <jats:italic>HOXA<\/jats:italic>\n                    cluster in AML cells with the common NPM1c mutation, which express both\n                    <jats:italic>HOXA<\/jats:italic>\n                    and\n                    <jats:italic>HOXB<\/jats:italic>\n                    genes. CTCF binding at the\n                    <jats:italic>HOXA<\/jats:italic>\n                    locus is conserved across primary AML samples, regardless of\n                    <jats:italic>HOXA<\/jats:italic>\n                    gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutant primary AML samples. Profiling of the three-dimensional chromatin architecture in primary AML samples with the NPM1c mutation identified chromatin loops between the\n                    <jats:italic>HOXA<\/jats:italic>\n                    cluster and loci in the\n                    <jats:italic>SNX10<\/jats:italic>\n                    and\n                    <jats:italic>SKAP2<\/jats:italic>\n                    genes, and an intergenic region located 1.4\u2009Mbp upstream of the\n                    <jats:italic>HOXA<\/jats:italic>\n                    locus. Deletion of CTCF binding sites in the\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutant OCI-AML3 AML cell line reduced multiple long-range interactions, but resulted in CTCF-independent loops with sequences in\n                    <jats:italic>SKAP2<\/jats:italic>\n                    that were marked by enhancer-associated histone modifications in primary AML samples.\n                    <jats:italic>HOXA<\/jats:italic>\n                    gene expression was maintained in CTCF binding site mutants, indicating that transcriptional activity at the\n                    <jats:italic>HOXA<\/jats:italic>\n                    locus in\n                    <jats:italic>NPM1<\/jats:italic>\n                    -mutant AML cells may be sustained through persistent interactions with\n                    <jats:italic>SKAP2<\/jats:italic>\n                    enhancers, or by intrinsic factors within the\n                    <jats:italic>HOXA<\/jats:italic>\n                    gene cluster.\n                  <\/jats:p>","DOI":"10.1038\/s41375-020-0856-3","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T15:03:31Z","timestamp":1589295811000},"page":"404-416","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Contribution of CTCF binding to transcriptional activity at the HOXA locus in NPM1-mutant AML cells"],"prefix":"10.1038","volume":"35","author":[{"given":"Reza","family":"Ghasemi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Struthers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5314-3043","authenticated-orcid":false,"given":"David H.","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"856_CR1","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/leu.2015.6","volume":"29","author":"D Spencer","year":"2015","unstructured":"Spencer D, Young M, Lamprecht T, Helton N, Fulton R, O\u2019Laughlin M, et al. 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