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

KMT2D+/bGeoation 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 KMT2D+/bGeoation 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. Rescue of genome wide chromatin abnormality, which has been reported in KMT2D+/bGeo mice, was evaluated by high throughput next generation sequencing following chromatin immunoprecipitation of H3K4me1 and H3K4me3. 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.