GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE255nnn/GSE255263/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE255263GEOGSEfalseGenome-wide maps of transcriptomic and epigenomic state in melanoma cell linesA mechanistic relationship between tumor epigenetic plasticity and nongenetic adaptive resistance to therapy is described, with MAPK inhibition of BRAF-mutant melanoma cells providing the model system. Upon inhibition, these largely melanocytic cells undergo reversible cell-state changes, ultimately yielding a drug-resistant mesenchymal-like phenotype. Epigenomic and transcriptomic kinetic studies, coupled with information theory and dynamic system modeling, revealed that, after just 3-days of treatment, RelA drives chromatin remodeling to establish an epigenetic program encoding long-term phenotype changes. Specifically, RelA transcriptionally inhibits SOX10 and NFKBIE through recruiting KDM5B and HDAC1 to down-regulate histone marks H3K4me3 and H3K27ac at their promoter regions. Suppression of SOX10 mediates melanoma regression towards drug-refractory phenotypes. These findings were confirmed in melanoma patients under MAPK inhibitor treatment, providing mechanistic insights into resistance-leading epigenetic reprogramming triggered following drug exposure.2026/03/31GSE255263GSM8067759GSM8067758GSM8067769GSM8067771GSM8067760GSM8067770GSM8067762GSM8067761GSM8067772GSM8067764GSM8067763GSM8067766GSM8067755GSM8067765GSM8067757GSM8067768GSM8067767GSM806775616791255263Homo sapiens