GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302057/primary200OKGenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302057GEOGSEfalseExamine the epigenetic consequences of KMT2D loss in melanoma using ChIP-seq profilingCellular 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.2026/07/04GSE302057GSM9095125GSM9095126GSM9095116GSM9095127GSM9095117GSM9095118GSM9095119GSM9095120GSM9095121GSM9095122GSM9095123GSM909512419057302057Mus musculus