EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells.[DND41_ChIP-seq]

Purpose: To investigate the mechanisms of 3D genome organization in drug-resistant T-ALL Methods: We used multiple epigenomics, chromatin conformation, and transcriptomic assays to study the mechanisms of chromatin adaptation in GSI-sensitive and GSI-resistant T-ALL Results: We report here that T/B cell lineage determining transcription factors are differentially expressed in GSI-resistant T-ALL cells, driving enhancer switching and genome folding reorganization events to promote GSI-resistance. Conclusions: These observations suggest a general mechanism that diffenrential activity of pioneering factors can be exploited to evade addiction to oncogenic signals. Overall design: ChIP-seq was performed in DMSO-treated parental, 24-hour GSI-treated parental, GSI-resistant, DMSO-treated reversed, and 24-hour GSI-treated reversed DND41 cells in duplicates.