Global Gene Expression Changes in Liver Following Hepatocyte Nuclear Factor 4 alpha deletion in Adult Mice

Hepatocyte nuclear factor 4 alpha (HNF4α) is known as the master regulator of hepatic differentiation, which regulates over 60% of the hepatocyte specific genes. Recent studies including this (Walesky et al. Am J Physiol Gastrointest Liver Physiol. 304:G26-37, 2013) demonstrated that HNF4α also inhibits hepatocyte proliferation via repression of pro-mitogenic genes. In this study hepatocyte specific HNF4α knockout mice were generated using 2-3 month old HNF4α-floxed mice treated with Cre recombinase under Major Urinary Protein promoter delivered in AAV8 vector (MUP-iCre-AAV8). Control mice were treated with MUP-EGFP-AAV8. Livers were isolated from control and KO mice one week after AAV8 administration and used for gene array analysis. These data revealed several new negative target genes of HNF4α, majority of which are pro-mitogeneic genes inhibited by HNF4α in adult hepatocytes.