Differential gene expression in mice with inducible loss of Bmal1 and HNF4a in the liver

Hepatocyte Nuclear Factor 4 alpha (HNF4a), a master regulator of hepatocyte differentiation, and circadian regulator Aryl Hydrocarbon-Like Receptor-Like 1 (ARNTL, or BMAL1) though robustly co-expressed in healthy liver, are incompatible within the context of HCC. Differential expression of Bmal1 and Hnf4a may control susceptibility to liver disease and ultimately, hepatocellular carcinoma. We compared gene expression profiles under conditions of inducible loss of hepatic Hnf4a and inducible loss of Hnf4a and Bmal1 in this RNA-seq experiment. Hepatic Hnf4a (H-KO) or Hnf4a and Bmal1 (BH-KO) were inducibly knocked out after 5 days tamoxifen treatment in eight week-old mice (H-KO) or (BH-KO) followed by vivarium chow or high fat feeding (BH-HF-KO). Littermate control mice (H-WT, BH-WT and BH-HF-WT ) were also treated with tamoxifen at eight weeks of age, but since they lacked the Cre transgene, Hnf4a and Bmal1 expression remained intact. Livers were harvested at 10 weeks of age (BH-WT/KO, H-WT/KO) or 45 weeks ( BH-HF-WT/KO) of age after high fat diet feeding, and liver tissue was flash frozen in liquid nitrogen. Overall design: Liver RNA-seq samples were prepared from liver harvested at the ZT8 time point (3:00 PM). Three biological replicates were used for each of the six conditions, resulting in 18 total samples.