GSE119244
HP1 are dispensable for liver development and functions but are essential to prevent liver tumorigenesis
Chromatin organization is known to play essential roles in cell identity and functions. Here, by hepatocyte-specific inactivation of all the genes encoding for HP1 proteins (HP1a, ß and ?) within mice livers (HP1-TKO mice), we demonstrate that these proteins are dispensable for hepatocyte development, survival and functions and for liver development but are critical to prevent liver tumorigenesis. We further showed that the lack of HP1 leads to the loss of heterochromatin hallmarks and to the deregulation of many genes with liver-specific functions. Furthermore, HP1-TKO transcriptome is also characterized by a strong enrichment in genes encoding for members of the KRAB-ZFP family of transcriptional repressors and as a consequence by reactivation of several families of Endogenous Retrovirus (ERV) with some of them behaving either as enhancers or alternative promoters leading to deregulated expression of several genes in their vicinity. Overall design: Examination of the liver transcriptome between mice controls and mice triple KO for the HP1 proteins (TKO)