Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate Determination

Vivian T. Thieu, Qing Yu, Hua Chen Chang, Norman Yeh, Evelyn T. Nguyen, Sarita Sehra, Mark Kaplan

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Transcriptional regulatory networks direct the development of specialized cell types. The transcription factors signal tranducer and activator of transcription 4 (Stat4) and T-bet are required for the interleukin-12 (IL-12)-stimulated development of T helper 1 (Th1) cells, although the hierarchy of activity by these factors has not been clearly defined. In this report, we show that these factors did not function in a linear pathway and that each factor played a unique role in programming chromatin architecture for Th1 gene expression, with subsets of genes depending on Stat4, T-bet, or both for expression in Th1 cells. T-bet was not able to transactivate expression of Stat4-dependent genes in the absence of endogenous Stat4 expression. Thus, T-bet requires Stat4 to achieve complete IL-12-dependent Th1 cell-fate determination. These data provide a basis for understanding how transiently activated and lineage-specific transcription factors cooperate in promoting cellular differentiation.

Original languageEnglish
Pages (from-to)679-690
Number of pages12
JournalImmunity
Volume29
Issue number5
DOIs
StatePublished - Nov 14 2008

Fingerprint

STAT4 Transcription Factor
Th1 Cells
Interleukin-12
Transcription Factors
Gene Regulatory Networks
Genes
Chromatin
Gene Expression
T-box transcription factor TBX21

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate Determination. / Thieu, Vivian T.; Yu, Qing; Chang, Hua Chen; Yeh, Norman; Nguyen, Evelyn T.; Sehra, Sarita; Kaplan, Mark.

In: Immunity, Vol. 29, No. 5, 14.11.2008, p. 679-690.

Research output: Contribution to journalArticle

Thieu, Vivian T. ; Yu, Qing ; Chang, Hua Chen ; Yeh, Norman ; Nguyen, Evelyn T. ; Sehra, Sarita ; Kaplan, Mark. / Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate Determination. In: Immunity. 2008 ; Vol. 29, No. 5. pp. 679-690.
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