Luciferase Reporter Cell Line - HepG2

Liver X receptor α (LXRα) is known to control key genes involved in cholesterol metabolism, but the detailed molecular mechanisms underlying this regulation are not fully understood. They found that PARP1 activation in the liver inhibits LXRα activity and the expression of genes responsible for cholesterol disposal induced by a high-cholesterol diet (HCD). Mechanistically, activated PARP1 poly(ADP-ribosyl)ates LXRα, reducing its DNA binding capacity and preventing its recruitment to target promoters. Interestingly, unactivated PARP1 was essential for LXRα transactivation and promoter binding. Thus, PARP1 plays a dual role: its activation suppresses LXRα activity, while its unactivated state facilitates it. This highlights PARP1 as a crucial regulator of LXRα signaling and cholesterol metabolism in the liver.

Figure 1. The researchers demonstrated that poly(ADP-ribosyl)ation inhibits LXRα transactivation and target gene expression in HepG2 cells. They used luciferase reporter assays to show that treatments affecting poly(ADP-ribosyl)ation altered LXRα activity. (Zhang F, et al., 2020)