EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in TH1 cells

Abstract

Differentiation of naïve CD4 T cells toward the T helper 1 (T H1) and T helper 2 (TH2) fates involves the transcriptional repression and enhancement, respectively, of 114 and 1113, adjacent chromosome 11 genes encoding the canonical TH2 cytokines interleukin-4 and interleukin-13. Proper execution of this developmental fate choice during immune responses is critical to host defense and, when misregulated, leads to susceptibility to infectious microbes and to allergic and autoimmune diseases. Here, using chromatin immunoprecipitation and real time reverse transcription PCR we identify the Polycomb family histone methyltransferase EZH2 as the enzyme responsible for methylating lysine 27 of histone H3 at the Il4-Il13 locus of TH1 but not TH2 cells, implicating EZH2 in the mechanism of Il4 and Il13 transcriptional silencing. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.