Key regulatory roles of PRDM1 in human NK-cell differentiation and activation

PRDM1, encoding a transcription factor (TF), regulates plasma cell and CD8+ T-cell terminal differentiation and Th2 lineage specification, while its role in human NK-cell differentiation and homeostasis is largely unknown. Here, we employed a multi-omics approach to dissect the transcriptional control of PRDM1 on human NK-cells. We also employed the APEX2 proximity-based biotinylation method, which enables efficient biotin-labeling of proteins within ~20 nm radius. NK-cells expressing APEX2-tagged PRDM1 were cultured with feeders for 7 or 28 days for the analysis of proximity-labeled proteins. Of the 30 PRDM1-associated cofactors identified by RIME, 12 (40%) were also detected in the APEX2 assay. Consistent with the RIME assay, RUNX3, RUNX1, and CBF-β were also biotinylated by PRDM1- APEX2. A lot more cofactors were identified in the APEX2 experiment, including HDAC1/2, histone deacetylases present in multiple corepressor complexes, similar to a previous study in mouse plasmablasts.