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Polycomb Repressive Complex 1 subunit Cbx4 positively regulates effector responses in CD8 T cells

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE236487 | GEO | 2023/07/10

REPOSITORIES: GEO

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Knockdown and Overexpression of Cbx4 wild type and of a Cbx4 chromodomain mutant in human epidermal stem cells

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