GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301779/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301779GEOGSEfalseExamine the epigenetic consequences of KMT2D loss in melanoma using ChIP-seq profiling [CUT&Run]Cellular plasticity contributes to melanoma progression and resistance to treatment, but the epigenetic mechanisms driving these changes are not well understood. In a Braf-mutant mouse model, we show that loss of Kmt2d, an enzyme that adds H3K4me1 to enhancers, speeds up melanoma development and shifts cells toward a neural crest-like state. Using single-cell multiome analysis, we found that this shift is driven by increased activity of TFAP2 transcription factors, linked to changes at enhancer regions. Kmt2d loss also leads to a more immunosuppressive tumor environment, with higher levels of suppressive immune cells. This study provides the first genetic evidence that enhancer disruption plays a key role in cell identity changes in melanoma.2026/07/04GSE301779GSM9089559GSM9089570GSM9089571GSM9089560GSM9089572GSM9089561GSM9089577GSM9089566GSM9089555GSM9089567GSM9089556GSM9089568GSM9089557GSM9089569GSM9089558GSM9089573GSM9089562GSM9089574GSM9089563GSM9089575GSM9089564GSM9089565GSM9089554GSM908957619057301779Mus musculus