Transcriptomics

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H3K27me3 ChIP-seq of naïve CD4 T cells


ABSTRACT: Differentiation and activation of T cells require the activity of numerous histone lysine methyltransferases (HMT) that control the transcriptional T cell output. One of the most potent regulators of T cell differentiation is the HMT Ezh2. Ezh2 is a key enzymatic component of the Polycomb repressive complex 2 (PRC2) that silences gene expression by histone H3 di/tri-methylation at lysine 27. Surprisingly, in many cell types, including T cells, Ezh2 is localized in both the nucleus and the cytosol. Here we show the presence of a nuclear-like PRC2 complex in T cell cytosol and demonstrate a role of cytosolic PRC2 in T cell antigen receptor mediated signaling. We show that short-term suppression of PRC2 precludes TCR driven T cell activation in vitro. We also demonstrate that pharmacological inhibition of PRC2 in vivo greatly attenuates the severe T cell driven autoimmunity caused by Treg depletion. Our data reveal cytoplasmic PRC2 is one of the most potent regulators of T cell activation and points towards the therapeutic potential of PRC2 inhibitors for the treatment of T cell driven autoimmune diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE110598 | GEO | 2018/03/07

REPOSITORIES: GEO

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