Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA207

Poster Communications

Role of JmjC Histone Demethylase in the Development of Non-Alcoholic Fatty Liver Disease

D. JEONG1

1. Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Korea (the Republic of).


  • Figure 2. JHDM directly interacts with SREBP1c.(A) HEK293T cells were co-transfected with Flag-mSREBP1c, Flag/SBP-JHDM. Cell lysates were pulled down using streptavidin beads and the precipitated proteins were immunoblotted with SREBP1c antibody. (B) The top panel shows four domain of JHDM. HEK293T cells were co-transfected with Flag-mSREBP1c, Flag/SBP-JHDM domain fragments. Cell lysates were pulled down using streptavidin beads and the precipitated proteins were immunoblotted with SREBP1c antibody. P1, Plant homeodomain; P2, Jumonji-C domain; P3,P4, C-terminal domain. (C) The top panel shows three domain of SREBP1c. HEK293T cells were co-transfected with Flag-JHDM, Flag/SBP-SREBP1c domain fragments. Cell lysates were pulled down using streptavidin beads and the precipitated proteins were immunoblotted with Flag antibody. S1, Transactivation domain; S2, Zinc-Finger domain; S3, helix-loop-helix leucine zipper domain.

Non-alcoholic fatty liver disease (NAFLD) is caused by excessive fat accumulation in the hepatocytes. Mild steatosis may develop into aggressive forms of NAFLD including hepatic fibrosis, cirrhosis and carcinoma. Sterol Regulatory element-binding transcription factor 1c (SREBP1c) is master transcription factor of the lipogenesis and the major regulators of NAFLD. JHDM, a JmjC histone demethylase, is known as the demethylase of the Histone H3K9 while it binds to H3K4me3 with the Plant-Homeodomain (PHD). In the current study, JHDM can bind and directly demethylate target protein. JHDM is known to have associated with metabolism-related transcription factors. In this study, we investigated the role of JHDM in the progression of NAFLD. For in vivo study, WT and JHDM overexpressed TG mice were fed normal diet or high fat diet for 8 weeks. And then, liver steatosis and blood chemistry were analyzed. Interestingly body weight and fat content was significantly decreased in TG mice and hepatic steatosis was improved. In HepG2 cells, overexpression of JHDM decreases SREBP1c protein and mRNA level and target gene mRNA of SREBP1c. JHDM knockdown using siRNA increases endogenous SREBP1c protein and mRNA level and target gene mRNA level of SREBP1c. H3K9 demethylation is regarded as transcription-active, we considered another effects of JHDM. Using immunoprecipitation, we tested protein interaction between JHDM and SREBP1c. JHDM directly interacts with SREBP1c at PHD domain of JHDM and Helix-loop-Helix domain of SREBP1c. In addition, we found that overexpression of JHDM attenuates lipid accumulation through oil red o staining. These results suggest that JHDM plays a role as a repressor in the progression of NAFLD through the association with SREBP1c.

Where applicable, experiments conform with Society ethical requirements