[PDF][PDF] Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination

VT Thieu, Q Yu, HC Chang, N Yeh, ET Nguyen… - Immunity, 2008 - cell.com
VT Thieu, Q Yu, HC Chang, N Yeh, ET Nguyen, S Sehra, MH Kaplan
Immunity, 2008cell.com
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 …
Summary
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.
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