EZH2-Mediated Epigenetic Regulation of NK Cell Expansion, Survival, and Effector Function [CUT&Run]

During this process, we observed with great precision that all ex vivo expanded NK cells upregulated the expression of the epigenetic regulator EZH2 (enhancer Zeste homolog 2). EZH2 acts canonically as the catalytic core of the Polycomb Repressive Complex 2 (PRC2), mediating H3K27 trimethylation and transcriptional repression.

While non-canonically, it also functions as a coactivator to promote gene expression. However, the regulatory role and function of EZH2 in NK cell expansion remained unclear. Here, by establishing a PBNK-derived NK cell expansion system, combining with the mRNA-seq and CUT&RUN-seq, we deeply characterize the dynamics of EZH2 and H3K27me3 binding, along with gene expression changes, between resting and expanded NK cells, and to infer the regulatory mechanisms employed by EZH2.