A deregulated m⁶A writer complex axis driven by BRD4 confers an epitranscriptomic vulnerability in combined DNA repair-targeted therapy.

ABSTRACT: Aberrant transcripts expression of the m⁶A methyltransferase complex (MTC) is widely found across human cancers, suggesting a dysregulated signaling cascade which integrates m⁶A epitranscriptome to drive tumorigenesis. However, the responsible transcriptional machinery directing the expression of distinct MTC subunits remains unclear. Here, we identified an unappreciated interplay between the histone acetyl-lysine reader BRD4 and the m⁶A writer complex across human cancers. BRD4 directly stimulates transcripts expression of seven MTC subunits, allowing the maintenance of the nuclear writer complex integrity. Upon BET inhibition, this BRD4-MTC signaling cascade accounts for global m⁶A reduction and the subsequent dynamic alteration of BRD4-depende

SUBMITTER: Lu X 

PROVIDER: S-EPMC10576145 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature