Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming
- 15 September 2009
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 183 (6), 3839-3847
- https://doi.org/10.4049/jimmunol.0901411
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.Keywords
This publication has 36 references indexed in Scilit:
- Signal Transducer and Activator of Transcription 4 Is Required for the Transcription Factor T-bet to Promote T Helper 1 Cell-Fate DeterminationImmunity, 2008
- Tpl2 kinase regulates T cell interferon-γ production and host resistance to Toxoplasma gondii The Journal of Experimental Medicine, 2008
- T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune toleranceNature, 2008
- STAT4and the Risk of Rheumatoid Arthritis and Systemic Lupus ErythematosusNew England Journal of Medicine, 2007
- Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencingNature Methods, 2007
- Stat4 limits DNA methyltransferase recruitment and DNA methylation of the IL-18Rα gene during Th1 differentiationThe EMBO Journal, 2007
- Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rβ2 expression during human Th1 cell differentiationThe EMBO Journal, 2007
- T helper type 1–specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-γ promoter are Stat4 dependentThe Journal of Experimental Medicine, 2006
- WebLogo: A Sequence Logo Generator: Figure 1Genome Research, 2004
- Genome-Wide Location and Function of DNA Binding ProteinsScience, 2000