Polycomb Repressive Complex 1 subunit Cbx4 positively regulates effector responses in CD8 T cells
Cytotoxic T lymphocyte (CTL) differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Fully uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. Here, we show that Polycomb Repressive Complex (PRC)1 subunit Chromobox (Cbx)4 favors effector CTL differentiation in murine model. Cbx4 deficiency in CTLs induced transcriptional signature and phenotype of memory cells, increasing the memory CTL population during acute viral infection. It has been previously shown that besides binding to H3K27me3 through its chromodomain, Cbx4 function as a SUMO E3 ligase in a SUMO interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in a SIM-dependent way and partially through its chromodomain. Our data revealed a novel role of a Polycomb group protein Cbx4 controlling CTL differentiation and indicates the SUMOylation as a key molecular mechanism connected to chromatin modification in this process. Overall design: To investigate the contribution of Cbx4 to the regulation of CD8 T cell transcriptional profile, in vitro-activated P14 Thy1.1+ CD8 T cells transduced with retrovirus expressing control shRNA or shRNA targeting Cbx4 were adoptively transferred to congenic receptor mice subsequently infected in acute LCMV infection model. Adoptively transfered transduced P14 CD8 T cells were sort-purified (Thy1.1+Ametrine+) by FACS on day 8 post-infection from the spleen of receptor mice and total RNA was extracted for RNA-Seq.