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E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment
University of Chicago, IL USA .
University of Chicago, IL USA .
University of Chicago, IL USA .
University of Chicago, IL USA .
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2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 9, 1534-1542 p.Article in journal (Refereed) Published
Abstract [en]

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.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-95981DOI: 10.1182/blood-2012-08-1449447ISI: 000321750300015OAI: oai:DiVA.org:liu-95981DiVA: diva2:639997
Note

Funding Agencies|National Institutes of Health|R01 CA099978R01 AI079213R21 AI096530|Leukemia & Lymphoma Society||University of Chicago|T32 GM07281||T32 GM38663||R01 CA099978-S1|

Available from: 2013-08-12 Created: 2013-08-12 Last updated: 2017-12-06

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Sigvardsson, Mikael

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf