{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:41:09Z","timestamp":1781106069842,"version":"3.54.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"29","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P018440\/1"],"award-info":[{"award-number":["MR\/P018440\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007903","name":"Bloodwise","doi-asserted-by":"publisher","award":["14032"],"award-info":[{"award-number":["14032"]}],"id":[{"id":"10.13039\/501100007903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Bone marrow failure (BMF) syndromes are inherited life-threatening conditions characterized by low blood cell production and predisposition to cancer. In this study we report a germ line frameshift variant in the Sp1 transcription factor in a family of patients with BMF and acute leukemia. Sp1 is ubiquitously expressed in human tissues and regulates transcription for blood cell lineage specification. Dissecting the molecular function of this\n                    <jats:italic>SP1<\/jats:italic>\n                    variant revealed a hypermorphic effect, triggering superactivation of Sp1-mediated transcription in the patients\u2019 blood. To our knowledge, this is the first report of a naturally occurring germ line variant in\n                    <jats:italic>SP1<\/jats:italic>\n                    that alters transcriptional networks and disrupts hematopoiesis in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2002857117","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T17:35:19Z","timestamp":1594143319000},"page":"17151-17155","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure"],"prefix":"10.1073","volume":"117","author":[{"given":"Hemanth","family":"Tummala","sequence":"first","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-8808","authenticated-orcid":false,"given":"Amanda J.","family":"Walne","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Findlay","family":"Bewicke-Copley","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"},{"name":"Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8490-8512","authenticated-orcid":false,"given":"Alicia","family":"Ellison","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"Pontikos","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-490X","authenticated-orcid":false,"given":"Maria G.","family":"Bridger","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6733-9752","authenticated-orcid":false,"given":"Ana","family":"Rio-Machin","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin K.","family":"Sidhu","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hasle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude","family":"Fitzgibbon","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Vulliamy","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderjeet","family":"Dokal","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1179\/1024533215Z.000000000381"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1803275115"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90053-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.10.4955"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2005.01.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80243-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21222"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-593343"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90594-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.7.2639"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.106054"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094450"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315034111"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.09.027"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90606-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.9.1646"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0517-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.07.016"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2555"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-019-0282-9"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/13793"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041331"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-336537"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3177"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120854"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.4.1676"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80472-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.5.2437"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9840"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx147"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0506-500"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2002857117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2002857117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:58:45Z","timestamp":1649829525000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2002857117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,7]]},"references-count":35,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2020,7,21]]}},"alternative-id":["10.1073\/pnas.2002857117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2002857117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,7]]},"assertion":[{"value":"2020-07-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}