Histone methyltransferase G9a protects against acute liver injury through GSTP1.

ABSTRACT: Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS- or APAP overdose-induced acute liver injury. Under D-galactosamine sensitization, liver-specific G9a-deficient mice (L-G9a^-/-) exhibited 100% mortality after LPS injection, while the control and L-G9a^+/- littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a^-/- mice displayed more severe liver injury. Mechanistically

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7206029 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature