Developmentally regulated isoform of HNF4α reprograms the adult liver

Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver in fed conditions. Both P1- and P2-HNF4α are expressed in fetal liver. P2-HNF4α expression is increased in fasted conditions, high fat diet, alcoholic liver and liver cancer. To determine the target genes of the P1- and P2-HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice (a7HMZ) to wildtype (WT) male mice. Liver ChIP-seq samples were taken at 10:30 AM (ZT 3.5) Liver ChIP-seq samples from adult WT (P1-HNF4a1) and a7HMZ (P2-HNF4a7) male mice were analyzed in triplicate at 10:30 AM (ZT 3.5).