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

Richart, Laia; Carrillo, Enrique; Río Machín, Ana; de Andrés, Mónica P.; Cigudosa, Juan C.; Sánchez-Arévalo Lobo, Víctor J.; Real, Francisco X.

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

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dc.contributor.author Richart, Laiaca
dc.contributor.author Carrillo, Enriqueca
dc.contributor.author Río Machín, Anaca
dc.contributor.author de Andrés, Mónica P.ca
dc.contributor.author Cigudosa, Juan C.ca
dc.contributor.author Sánchez-Arévalo Lobo, Víctor J.ca
dc.contributor.author Real, Francisco X.ca
dc.date.accessioned 2016-01-19T15:57:19Z
dc.date.available 2016-01-19T15:57:19Z
dc.date.issued 2016
dc.description.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.ca
dc.description.sponsorship This work was supported, in part, by grants from Ministerio de Economía y Competitividad, Madrid, Spain (SAF2007–60860, SAF2011–29530 and ONCOBIO Consolider), Instituto de Salud Carlos III, Madrid, Spain (RTICC RD12/0036/0034), European Union Seventh Framework Programme (grant 256974), and an EIN/Roche-CNIO collaborative grant to F.X.R.; and grants from Instituto de Salud Carlos III (INTRASALUD PI12/00425 and RTICC RD12/0036/0037) to J.C.C
dc.format.mimetype application/pdfca
dc.identifier.citation Richart L, Carrillo-de Santa Pau E, Río-Machín A, de Andrés MP, Cigudosa JC, Lobo VJ et al. BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis. Nature communications. 2016;7:10153. DOI: 10.1038/ncomms10153ca
dc.identifier.doi http://dx.doi.org/10.1038/ncomms10153
dc.identifier.uri http://hdl.handle.net/10230/25604
dc.language.iso engca
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Nature communications. 2016;7:10153
dc.rights © Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the materialca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0ca
dc.subject.other Genèticaca
dc.subject.other Tumorsca
dc.title BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesisca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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