ArrayExpress Uploader0mouseC57BL/6J wild typeTh1 growth conditionsC57BL6-STAT4<tm1> (STAT4 knock out)Th1 growth conditionsC57BL/6J wild typeTh2 growth conditionsB6.129S2STAT6<tm1Gru>/J (STAT6 knock out)Th2 growth conditions6106arrayexpress_sid6Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however,...E-GEOD-22081/profile/8773/arrayexpressuploader24cellcell phenotypechromatingenomehistoneDec.12, 2014Falsetranscription-profiling-by-array-of-mouse-wild-typE-GEOD-22081_A-AFFY-45Transcription profiling by array of mouse wild type, STAT4 knock out or STAT6 knockout CD4-positive T cellsNov.11, 2014Signal 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. Affymetrix Mouse Genome 430 2.0 Arrays were used to evaluate global gene expression.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22081http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22081/samples/