title: Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions.
abstract: Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hif1a) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.
authors.affiliation: Signal Transduction, German Rheumatism Research Center (DRFZ), Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jargosch
authors.affiliation: Knowledge Management in Bioinformatics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kröger
authors.affiliation: Signal Transduction, German Rheumatism Research Center (DRFZ), Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Gralinska
authors.affiliation: Signal Transduction, German Rheumatism Research Center (DRFZ), Berlin, Germany.|Bioinformatics Group, University of Potsdam, Potsdam, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Klotz
authors.affiliation: Signal Transduction, German Rheumatism Research Center (DRFZ), Berlin, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Scientific Genomics Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Knowledge Management in Bioinformatics, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Leser
authors.affiliation: Bioinformatics Group, University of Potsdam, Potsdam, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Selbig
authors.affiliation: Bioinformatics Group, University of Potsdam, Potsdam, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Groth
authors.affiliation: Signal Transduction, German Rheumatism Research Center (DRFZ), Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Baumgrass
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D053263:Gene Regulatory Networks; D051379:Mice; D018121:Receptors, Cytokine / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018511:Systems Integration; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse