Anterograde Regulation of Nuclear-encoded Mitochondrial Genes and FGF21 Signaling by Hepatic Histone Demethylase LSD1 [RNA-seq]

Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than one thousand nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain fully elucidated. Here we show that histone demethylase LSD1 knockout from adult mouse liver (LSD1-LKO) reduces one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function. ChIP-seq analysis shows that LSD1 and LSD1-targeted H3K4me2 modulate the expression of mitochondrial genes in liver. RNA-seq analysis of gene expression in liver of LSD1-LKO and controls. To generate LSD1-LKO mice, AAV8-TBG-cre was injected through tail vein into LSD1-lox/lox mice at 6-7 weeks of age. AAV8-TBG-GFP was injected to LSD1-lox/lox mice as controls. One week after the injections, the mice were fed a high fat diet for 12 weeks.