LXRs participate in the fasting response by assisting C/EBPβ binding to enhancers and promoting the fasting transcriptional program [ATAC-Seq]

Profiling the genome-wide profile of LXRα by ChIP-seq showed it directly binds enhancers activated by it. Surprisingly, we found that LXRs assist the binding of CCAAT/enhancer binding protein beta (C/EBPβ) to enhancers during fasting. C/EBPβ is a key TF regulating the fasting response and its binding was profoundly perturbed in the lack of LXRs across the genome.

The cooperation between LXRs and C/EBPβ promoted fasting-dependent gene induction. These findings unravel a role for LXRs in the fasting response whereby LXRs bind and activate enhancers, assist C/EBPβ binding and promote gene induction. This shows the complex cooperation of TFs in regulating gene expression to maintain homeostasis during fasting and places LXRs as novel regulators of the fasting response.