Genomics

Dataset Information

0

Genome-wide maps of transcriptomic and epigenomic state in melanoma cell lines


ABSTRACT: A 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE134459 | GEO | 2019/09/23

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2014-01-04 | E-GEOD-50535 | biostudies-arrayexpress
2014-01-04 | GSE50535 | GEO
| phs000977 | dbGaP
2022-12-08 | GSE211906 | GEO
2015-03-05 | GSE60665 | GEO
2015-03-05 | GSE60664 | GEO
2015-03-05 | GSE60663 | GEO
2024-04-24 | GSE256464 | GEO
2024-08-26 | GSE254326 | GEO
2023-08-24 | GSE221241 | GEO