Multi-omics study to dissect the transcriptional control of PRDM1 in human NK-cells

PRDM1 has been shown to be expressed throughout NK-cell development, and its expression has been demonstrated to be important for NK cell maturation in mouse. It is also a tumor suppressor that is frequently inactivated/lost in NK-cell malignancies. Here we conducted an extensive study on PRDM1 regulation in human NK cells cultured at different conditions that showed quite different growth. NK-cells were able to rapidly proliferate with low apoptosis for more than a month with feeder cells, while IL-2 alone could only maintain human NK cell survival in vitro with limited proliferation for about a week. By comparing binding of PRDM1, difference in chromatin accessibility and gene expression between the two conditions through ChIP-seq, ATAC-seq, and RNA-seq, we investigated the regulatory role of PRDM1 in human NK cells. In addition, we also did knockout and overexpression of PRDM1 in human NK cells and KHYG1 cell line to investigate gene expression regulation by the PRDM1.