Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming

Seth R. Good, Vivian T. Thieu, Anubhav N. Mathur, Qing Yu, Gretta L. Stritesky, Norman Yeh, John T. O'Malley, Narayanan B. Perumal, Mark H. Kaplan

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

STAT4 is a critical component in the development of inflammatory adaptive immune responses. It has been extensively characterized as a lineage-determining factor in Th1 development. However, the genetic program activated by STAT4 that results in an inflammatory cell type is not well defined. In this report, we use DNA isolated from STAT4-chromatin immunoprecipitation to perform chromatin immunoprecipitation-on-chip analysis of over 28,000 mouse gene promoters to identify STAT4 targets. We demonstrate that STAT4 binds multiple gene-sets that program distinct components of the Th1 lineage. Although many STAT4 target genes display STAT4-dependent IL-12-inducible expression, other genes displayed IL-12-induced histone modifications but lack induction, possibly due to high relative basal expression. In the subset of genes that STAT4 programs for expression in Th1 cells, IL-12-induced mRNA levels remain increased for a longer time than mRNA from genes that are not programmed. This suggests that STAT4 binding to target genes, while critical, is not the only determinant for STAT4-dependent gene programming during Th1 differentiation.

Original languageEnglish (US)
Pages (from-to)3839-3847
Number of pages9
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Good, S. R., Thieu, V. T., Mathur, A. N., Yu, Q., Stritesky, G. L., Yeh, N., O'Malley, J. T., Perumal, N. B., & Kaplan, M. H. (2009). Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming. Journal of Immunology, 183(6), 3839-3847. https://doi.org/10.4049/jimmunol.0901411