Hexokinase 2 and lactate mediated gene expression via histone H3 lysine 18 lactylation (CHO CUT&Tag)

Hexokinase catalyzes the first committed step in glucose metabolism by phosphorylating glucose to produce glucose-6-phosphate. Highly glycolytic proliferating cells such as cancer cells take advantage of HK2 expression to accelerate glucose metabolism even in the presence of oxygen. This acceleration not only provides sufficient glycolytic intermediates to support the anabolic demands of the cells but also inevitably accompanies increased formation of metabolic end products such as lactate. Currently, the effect of lactate caused by HK2-mediated metabolic alteration is largely unknown. A recent study found that lactate plays a role in an epigenetic alteration known as histone lactylation. Here, using RNA-seq and CUT&Tag chromatin profiling, we study the effect of HK2 and lactate on gene expression via histone lactylation (H3K18la). Overall design: Genomic occupancy profiling of H3K18la and H3K18ac for hexokinase null (EV), wildtype HK2 (WTHK2), kinase-dead mutant HK2 (SAHK2) expressing cells.