c-MYC oncogene is deregulated in most human tumors. Histone marks associated with transcriptionally active genes define high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are unknown.
Researchers report that c-MYC interacts with BPTF, a core subunit of the NURF chromatin-remodelling complex. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts.
BPTF knockdown leads to decreased c-MYC recruitment to DNA and changes in chromatin accessibility. In Bptf-null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1–S progression and replication stress, but not for c-MYC-driven apoptosis.
Bioinformatics analyses unveil that BPTF levels correlate positively with c-MYC-driven transcriptional signatures.
In vivo, Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumor development and extends survival.
These findings uncover BPTF as a crucial c-MYC co-factor required for its biological activity and suggest that the BPTF-c-MYC axis is a potential therapeutic target in cancer.