PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [ChIP-Seq]

The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters. H3K27me3 ChIP in time-course of P14 and M2 hepatocytes. P14 replicates include 2 male and 2 female.