Identification of elements driving KIR gene demethylation in CD56-Bright NK cells

Understanding the timing and mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells in vitro. Previous studies revealed that a central RUNX-binding site is a key element required for the demethylation and activation of the KIR proximal promoter.

RUNX proteins associate with the TET family of proteins that generate 5‑hydroxymethylcytosine (5hmC) and drive DNA demethylation. We employed a novel system capable of distinguishing 5‑methylcytosine (5mC) and 5hmC residues in DNA to provide insight into the process of KIR gene activation during NK cell development. Significant levels of 5hmC, indicative of TET activity, were observed in variegated KIR genes in CD56Bright NK cells but not the preceding ILCP or subsequent CD56-Dim stages of development.