Developmentally regulated isoform of HNF4a reprograms the adult liver

Hepatocyte Nuclear Factor 4a (HNF4a), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4a but not P2-HNF4a is expressed in normal adult liver while both P1- and P2-HNF4a are expressed in fetal liver and liver cancer. To determine the physiological function of the HNF4a isoforms, we compared P2-HNF4a-expressing exon swap mice to wildtype (WT) using RNA-seq, ChIP-seq, proteomics, protein binding microarrays (PBMs) and metabolomics. P2-HNF4a orchestrates a distinct transcriptomic and metabolomic profile. Overall design: Liver RNA-seq samples from both genotypes (WT and a7HMZ, P1- and P2-HNF4a respectively) were taken at three time-points as well as a 12-hr fast with both genotypes at the earliest time-point. Please note that three different time points are indicated in the sample titles as the time of the day, in 24hr notation (i.e. 1030 = 10:30am, 1330 = 1:30pm, and 2030 = 8:30pm).