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STAT4 ChIP-on-chip in IL12-Mediated T Helper 1 Cell Differentiation

ABSTRACT: The Signal Transducer and Activator of Transcription factor 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 ChIP-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. While 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. The supplementary bed file contains all 7504 Stat4 binding sites reported in the supplementary Analysis_results.xls Excel file.

ORGANISM(S): Mus musculus

PROVIDER: GSE16845 | GEO | 2009/06/26

SECONDARY ACCESSION(S): PRJNA117617

REPOSITORIES: GEO

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Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet

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Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet

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STAT4 and T-bet control follicular helper T cells development in viral infections [ATAC-seq]

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STAT4 and T-bet control follicular helper T cells development in viral infections [RNA-seq]

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Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during Helper T Cell Differentiation (ChIP-Seq)

Project description:Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription using cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper specification. The roles of STAT proteins to shape T helper cell phenotype was investigated by comparing DNA binding profiles of STAT4 and STAT6 in Th1 and Th2 conditions. The functional outcome of STAT bindings was further evaluated by profiling histone epigenetic marks and gene expression changes between WT and STAT-deficient T cells in Th1 and Th2 conditions.

2010-06-18 | E-GEOD-22104 | biostudies-arrayexpress

Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during Helper T Cell Differentiation (gene expression)

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