Figure 4.

The loss of EZH1 and EZH2 impaired functional performance, reduced survival, and decreased hepatocyte proliferation in E1/2KO mice during chronic liver injury induced by CCl₄ injections twice a week. A) Kaplan-Meier survival curves after fourth injection of CCl₄ to 3-mo-old mice show reduced survival in E1/2KO mice (n = 9 for each genotype). B) Representative immunofluorescence staining for cell proliferation marker Ki67 (red) of hepatocytes (arrows). Nuclei were counterstained with DAPI. Insets show higher magnifications of the boxed areas. Note that in E1/2KO livers, only nonparenchymal cells proliferate after the fourth CCl₄ injection. PV, portal vein. C) Quantification of Ki67-positive hepatocytes. The number of Ki67-positive cells was determined in 5 independent confocal images taken at ×200 magnification and expressed as numbers per field. Data are the mean ± sd (n = 3 mice for each genotype). **P < 0.01; ***P < 0.0001. D) H&E staining of WT and E1/2KO livers. E) Serum levels of total bilirubin and albumin 2 d after the first and fourth injection of CCl₄ to 3-mo-old mice. Data are the mean ± sd (n = 5 mice per each genotype per time point).