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Blood. 2013 Feb 28;121(9):1534-42. doi: 10.1182/blood-2012-08-449447. Epub 2013 Jan 7.

E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment.

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Committees on Cancer Biology and. Immunology, Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.


The E2A transcription factors promote the development of thymus-seeding cells, but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. Here, we showed that E2A proteins were required to promote T-lymphocyte commitment from DN2 thymocytes and to extinguish their potential for alternative fates. E2A proteins functioned in DN2 cells to limit expression of Gata3, which encodes an essential T-lymphocyte transcription factor whose ectopic expression can arrest T-cell differentiation. Genetic, or small interfering RNA-mediated, reduction of Gata3 rescued T-cell differentiation in the absence of E2A and restricted the development of alternative lineages by limiting the expanded self-renewal potential in E2A−/− DN2 cells. Our data support a novel paradigm in lymphocyte lineage commitment in which the E2A proteins are necessary to limit the expression of an essential lineage specification and commitment factor to restrain self-renewal and to prevent an arrest in differentiation.

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