{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:26:49Z","timestamp":1787016409054,"version":"build-2736575974"},"reference-count":54,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"48","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,11,29]]},"abstract":"<jats:p>\n                    Loss-of-function studies have shown that transcription factor T cell factor-1 (TCF1), encoded by the\n                    <jats:italic>Tcf7<\/jats:italic>\n                    gene, is essential for T cell development in the thymus. We discovered that the\n                    <jats:italic>Tcf7<\/jats:italic>\n                    expression level is regulated by E box DNA binding proteins, independent of Notch, and regulates \u03b1\u03b2 and \u03b3\u03b4 T cell development. Systematic interrogation of the five E protein binding elements (EPE1\u20135) in the\n                    <jats:italic>Tcf7<\/jats:italic>\n                    enhancer region showed lineage-specific utilization. Specifically, loss-of-function analysis revealed that only EPE3 plays a critical role in supporting \u03b1\u03b2 T cell development, while EPE1, 3, and 5 regulate the \u03b3\u03b4 T cell maturation and functional cell fate decision. The importance of EPE3 in supporting both lineages may stem from its unique capacity to interact with the\n                    <jats:italic>Tcf7<\/jats:italic>\n                    transcriptional start site. Together, these studies demonstrate that the precise dosage of TCF1 expression mediated by distinct EPEs generates a balanced output of T cells from the thymus.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ado5982","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T14:01:25Z","timestamp":1732716085000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["TCF1 dosage determines cell fate during T cell development"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3039-1945","authenticated-orcid":true,"given":"Anjali","family":"Verma","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, 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