| First Author | Richart L | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10153 | PubMed ID | 26729287 |
| Mgi Jnum | J:235819 | Mgi Id | MGI:5803755 |
| Doi | 10.1038/ncomms10153 | Citation | Richart L, et al. (2016) BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis. Nat Commun 7:10153 |
| abstractText | c-MYC oncogene is deregulated in most human tumours. Histone marks associated with transcriptionally active genes define high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are unknown. Here we 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 tumour development and extends survival. Our 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. |
