Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.

Elo LL, Järvenpää H, Tuomela S, Raghav S, Ahlfors H, Laurila K, Gupta B, Lund RJ, Tahvanainen J, Hawkins RD, Oresic M, Lähdesmäki H, Rasool O, Rao KV, Aittokallio T, Lahesmaa R

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.

Chromatin Shearing

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June, 2010



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