BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis

Laia Richart, Enrique Carrillo- de Santa Pau, Ana Río-Machín, Mónica P. de Andrés, Juan C. Cigudosa, Víctor J. Sánchez-Arévalo Lobo () and Francisco X. Real ()
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Laia Richart: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO
Enrique Carrillo- de Santa Pau: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO
Ana Río-Machín: Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center-CNIO
Mónica P. de Andrés: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO
Juan C. Cigudosa: Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center-CNIO
Víctor J. Sánchez-Arévalo Lobo: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO
Francisco X. Real: Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10153

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