Program in Gene Function and Expression; Program in Molecular Medicine
Medical Subject Headings
Gene Expression Regulation; Hep G2 Cells; Histone Demethylases
Genetics and Genomics | Molecular Biology | Molecular Genetics
Aberrant gluconeogenic gene expression is associated with diabetes, glycogen storage disease, and liver cancer. However, little is known how these genes are regulated at the chromatin level. In this study, we investigated in HepG2 cells whether histone demethylation is a potential mechanism. We found that knockdown or pharmacological inhibition of histone demethylase LSD1 causes remarkable transcription activation of two gluconeogenic genes, FBP1 and G6Pase, and consequently leads to increased de novo glucose synthesis and decreased intracellular glycogen content. Mechanistically, LSD1 occupies the promoters of FBP1 and G6Pase, and modulates their H3K4 dimethylation levels. Thus, our work identifies an epigenetic pathway directly governing gluconeogenic gene expression, which might have important implications in metabolic physiology and diseases.
Rights and Permissions
Citation: PLoS One. 2013 Jun 5;8(6):e66294. doi: 10.1371/journal.pone.0066294. Print 2013. Link to article on publisher's site
Pan, Dongning; Mao, Chunxiao; and Wang, Yong-Xu, "Suppression of Gluconeogenic Gene Expression by LSD1-Mediated Histone Demethylation" (2013). Program in Gene Function and Expression Publications and Presentations. 218.