First Author | Xu W | Year | 2013 |
Journal | Blood | Volume | 121 |
Issue | 9 | Pages | 1534-42 |
PubMed ID | 23297135 | Mgi Jnum | J:194759 |
Mgi Id | MGI:5474705 | Doi | 10.1182/blood-2012-08-449447 |
Citation | Xu W, et al. (2013) E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment. Blood 121(9):1534-42 |
abstractText | 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. |