Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.
Elo
Laura L
LL
Biomathematics Research Group, Department of Mathematics, University of Turku, FI-20014 Turku, Finland.
Järvenpää
Henna
H
Tuomela
Soile
S
Raghav
Sunil
S
Ahlfors
Helena
H
Laurila
Kirsti
K
Gupta
Bhawna
B
Lund
Riikka J
RJ
Tahvanainen
Johanna
J
Hawkins
R David
RD
Oresic
Matej
M
Lähdesmäki
Harri
H
Rasool
Omid
O
Rao
Kanury V
KV
Aittokallio
Tero
T
Lahesmaa
Riitta
R
D002454:Cell Differentiation / Q000276:immunology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D055106:Genome-Wide Association Study; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology; D014158:Transcription, Genetic
D050800:STAT6 Transcription Factor; D015847:Interleukin-4