The effect of acute sustained hypoxia on gene expression in liver, kidney and lung on different times-of-day

Many hypoxia related diseases present a time of day dependency. Here, we examine the difference in transcriptional response to hypoxia (4h, 6% O2), in different times of day, namely the middle of the light phase and the middle of the dark phase. Additionally, many rhythmic processes in mammals are controlled by the circadian clock. to examine the dependency of the hypoxic response on the molecular circadian clock, we repeated the experiment under constant darkness regimen with either wild type mice or Per1,2 double knock out mice (which lack a functional clock), and sequenced the liver transcriptome. Overall design: The design contains 4 experimental conditions in light/dark regimen (LD): (1) 4h 21% O2 between ZT4-8, (2) 4h 6% O2 between ZT4-8, (3) 4h 21% O2 between ZT16-20, (4) 4h 6% O2 between ZT16-20. 4 biological replicates (mice) per condition. 3 tissues (liver, kidney, lung) were sequenced per mouse. For constant dark (DD) regimen, 8 conditions were used: (1) WT 21% O2 CT4-8, (2) WT 6% O2 CT4-8, (3), WT 21% O2 CT16-20, (4) WT 6% O2 CT16-20, (5) Per1,2 double knock-out (KO) 21% O2 CT4-8, (6) KO 6% O2 CT4-8, (7) KO 21% O2 CT16-20, (8) KO 6% O2 CT16-20. only liver RNA was sequenced in the constant dark design.