{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:48:08Z","timestamp":1790830088244,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["CA,119008"],"award-info":[{"award-number":["CA,119008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,9]]},"abstract":"<jats:p>\n                    Taspase1, a highly conserved threonine protease encoded by\n                    <jats:italic>TASP1<\/jats:italic>\n                    , cleaves nuclear histone-modifying factors and basal transcription regulators to orchestrate diverse transcription programs. Hereditary loss-of-function mutation of\n                    <jats:italic>TASP1<\/jats:italic>\n                    has recently been reported in humans as resulting in an anomaly complex syndrome, which manifests with hematological, facial, and skeletal abnormalities. Here, we demonstrate that Taspase1-mediated cleavage of TFIIA\n                    <jats:bold>\u03b1<\/jats:bold>\n                    -\n                    <jats:bold>\u03b2<\/jats:bold>\n                    , rather than of MLL1 or MLL2, in mouse embryos was required for proper fetal liver hematopoiesis and correct segmental identities of the axial skeleton. Homozygous genetic deletion of Taspase1 disrupted embryonic hematopoietic stem cell self-renewal and quiescence states and axial skeleton fates. Strikingly, mice carrying knockin noncleavable mutations of TFIIA\n                    <jats:bold>\u03b1<\/jats:bold>\n                    -\n                    <jats:bold>\u03b2<\/jats:bold>\n                    , a well-characterized basal transcription factor, displayed more pronounced fetal liver and axial skeleton defects than those with noncleavable MLL1 and MLL2, 2 trithorax group histone H3 trimethyl transferases. Our study offers molecular insights into a syndrome in humans that results from loss of TASP1 and describes an unexpected role of TFIIA\n                    <jats:bold>\u03b1<\/jats:bold>\n                    -\n                    <jats:bold>\u03b2<\/jats:bold>\n                    cleavage in embryonic cell fate decisions.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.149382","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T12:04:04Z","timestamp":1624363444000},"source":"Crossref","is-referenced-by-count":2,"title":["Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3161-8968","authenticated-orcid":true,"given":"Hidetaka","family":"Niizuma","sequence":"first","affiliation":[{"name":"Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA."},{"name":"Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1084-2415","authenticated-orcid":true,"given":"Adam C.","family":"Searleman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-9390","authenticated-orcid":true,"given":"Shugaku","family":"Takeda","sequence":"additional","affiliation":[{"name":"Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-3476","authenticated-orcid":true,"given":"Christopher Y.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU School of Medicine, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA."},{"name":"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-0551","authenticated-orcid":true,"given":"James J.","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, 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