Transcriptional adaptation and enhancer rewiring promote metabolic resistance in BRAFmutated multiple myeloma (ChIP-seq)

Purpose: We examined the mechanisms of transcriptional adaptation in persistent cells and asked if transcriptional state changes can be attributed to alterations in enhancer activity. Methods: ChIPseq for the enhancer mark H3K27ac was performed in three single-cell clones derived from the multiple myeloma cell line U266 treted with dabrafenib vs. DMSO for 14 Results: We observed substantial epigenetic remodeling illustrated by a greater number of unique peaks in dabrafenib-persistent cells as compared to dabrafenib-naïve controls. Out of a total of 22756 merged peaks, which were called in at least three samples, 7645 (34%) were unique to persistent cells compared to 454 (2%) in untreated cells. Conclusions: Altered transcriptional states are associated with enhancer rewiring in drug-resistant myeloma Overall design: ChIPseq for the enhancer mark H3K27ac was performed in three single-cell clones derived from the multiple myeloma cell line U266 treted with dabrafenib vs. DMSO for 14 days.