TY  - JOUR
A1  - Jargosch, M.
A1  - Kroeger, S.
A1  - Gralinska, E.
A1  - Klotz, Ulrike
A1  - Fang, Z.
A1  - Chen, W.
A1  - Leser, U.
A1  - Selbig, Joachim
A1  - Groth, Detlef
A1  - Baumgrass, Ria
T1  - Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions
JF  - Genetics and molecular research
N2  - 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 Hifla) 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.
KW  - Data integration
KW  - Th2 cells
KW  - Gene regulatory network
KW  - STAT6
KW  - Transcription factors
Y1  - 2016
U6  - https://doi.org/10.4238/gmr.15028493
SN  - 1676-5680
VL  - 15
PB  - FUNPEC
CY  - Ribeirao Preto
ER  -