title: Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
abstract: 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.
authors.affiliation: Biomathematics Research Group, Department of Mathematics, University of Turku, FI-20014 Turku, Finland.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Elo
authors.forename: Henna
authors.initials: H
authors.lastname: Järvenpää
authors.forename: Soile
authors.initials: S
authors.lastname: Tuomela
authors.forename: Sunil
authors.initials: S
authors.lastname: Raghav
authors.forename: Helena
authors.initials: H
authors.lastname: Ahlfors
authors.forename: Kirsti
authors.initials: K
authors.lastname: Laurila
authors.forename: Bhawna
authors.initials: B
authors.lastname: Gupta
authors.forename: Riikka J
authors.initials: RJ
authors.lastname: Lund
authors.forename: Johanna
authors.initials: J
authors.lastname: Tahvanainen
authors.forename: R David
authors.initials: RD
authors.lastname: Hawkins
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.forename: Omid
authors.initials: O
authors.lastname: Rasool
authors.forename: Kanury V
authors.initials: KV
authors.lastname: Rao
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: 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
chemical_list: D050800:STAT6 Transcription Factor; D015847:Interleukin-4