Circadian profiling of livers from control and hepatocyte-specific KLF10 knockout mice using RNA sequencing

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like transcription factors (KLFs) govern metabolic homeostasis in various organs and many members show a circadian expression. We previously showed that the transcription factor Kru¨ppel-like factor 10 (KLF10) is a clock-controlled gene in liver. To better understand the role of KLF10 in circadian physiology, we analyzed around the clock the hepatic transcriptome of mice lacking KLF10 specifically in hepatocytes. Livers of control and KLF10 conditional knockout mice entrained to a 12 h light: 12 h dark cycle were sampled every 3h for 24h. Total RNA from pools of 3 livers per time point was sequenced. Upon statistical analysis of time series for circadian rhythmicity we found that hepatocyte specific KLF10 knockout mice displayed a circadian transcriptome that differ from that of controls with genes showing an altered rhythmicity while other gained rhythmicity. Phase Set Enrichment Analysis further revealed that mutant mice displayed an altered temporal coordination of pathways related to energy metabolism.