TAK-418-418, a LSD1 inhibitor, can rescue the genome wide chromatin abnormality in hippocapmus tissue in KMT2D+/bGeo mice after 2 week treatment [RNA-seq]

Mutation in KMT2D, a histone-lysine N-methyl transferase, is responsible for majority of Kabuki syndrome in human. A mouse model of Kabuki syndrome with heterzygous mutation of KMT2D, KMT2D+/bGeo was created to understand the disease mechanism and for drug discovery. TAK-418-418, a lysine-specific histone demethylase (LSD1) inhibitor, was tested on these mice for therapeutic treatment of the disease. Differences between expression levels among different experimental conditions was evaluated by high throughput RNA sequencing (RNA-Seq). Overall design: Wild type mice and KMT2D+/bGeo mice were treated with either TAK-418-418 (3-4 per group) or vehicle control (3-4 per group) starting at age of 2-week old. Hippacampi were harvested at the end of 2-week treatment. Global chromatin changes were investigated by high throughput CHIPSEQ of H3K4me1 and H3K4me3.