E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment
2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 9, 1534-1542 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
American Society of Hematology , 2013. Vol. 121, no 9, 1534-1542 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-95981DOI: 10.1182/blood-2012-08-1449447ISI: 000321750300015OAI: oai:DiVA.org:liu-95981DiVA: diva2:639997
Funding Agencies|National Institutes of Health|R01 CA099978R01 AI079213R21 AI096530|Leukemia & Lymphoma Society||University of Chicago|T32 GM07281||T32 GM38663||R01 CA099978-S1|2013-08-122013-08-122013-08-12