%0 Journal Article
%T Dual function of polycomb group proteins in differentiated murine T helper (CD4+) cells
%A Eyal Jacob
%A Reut Hod-Dvorai
%A Or Ben-Mordechai
%A Yulia Boyko
%A Orly Avni
%J Journal of Molecular Signaling
%D 2011
%I Ubiquity Press
%R 10.1186/1750-2187-6-5
%X PcG proteins were knocked down in primary and established murine Th cells using transduction of lentiviruses encoding short hairpin RNAs (shRNAs) directed to Mel-18, Ezh2, Eed and Ring1A, representative of two different PcG complexes. The chromatin structure and the binding activity of PcG proteins and transcription factors at the Ifng promoter were assessed by chromatin immunoprecipitation (ChIP) assays.Downregulation of PcG proteins was consistent with their function as positive regulators of the signature cytokine genes in primary and established Th1 and Th2 cells. Moreover, the PcG protein Mel-18 was necessary to recruit the Th1-lineage specifying transcription factor T-bet, and the T cell receptor (TCR)-inducible transcription factor NFAT1 to the Ifng promoter in Th1 cells. Nevertheless, our results suggest that PcG proteins can function also as conventional transcriptional repressors in Th cells of their known target the Hoxa7 gene.Our data support a model whereby the non-differentially expressed PcG proteins are recruited in a Th-lineage specific manner to their target genes to enforce the maintenance of specific transcriptional programs as transcriptional repressors or activators. Although our results suggest a direct effect of PcG proteins in the regulation of cytokine gene expression, indirect functions cannot be excluded.When naive Th cells encounter an antigen for the first time, they can differentiate into the effector lineages Th1, Th2 and Th17 that differentially express cytokine genes [1-3]. The Th1 and Th2 lineages are characterized by the expression of the signature cytokines IFN¦Ã and IL-4, respectively. IFN¦Ã exerts protective functions in microbial infections and is observed clinically in cases of autoimmune diseases. IL-4 is strongly apparent in parasitic infections, and is associated with allergic reactions. The polarization of Th cells is most efficiently promoted by the cytokine milieu; IL-12 strongly potentiates the differentiation toward the
%K Il4
%K Ifng
%K T helper cells
%K polycomb
%K transcription factors: NFAT
%K T-bet
%U http://www.jmolecularsignaling.com/content/6/1/5