Genomics

Dataset Information

298

BPTF is required for c-MYC-induced remodelling of target chromatin and transcriptional activation [ChIP-Seq]


ABSTRACT: The c-MYC oncogene is a key transcription factor deregulated in most human tumors. Histone marks associated with transcriptionally active genes in euchromatic islands define the set of high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are not known but likely involve chromatin-remodelling and chromatin-modifying complexes. Here, we show that c-MYC interacts with BPTF, a core subunit of the NURF complex that binds active chromatin. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to a decrease in c-MYC recruitment to DNA and to changes in chromatin accessibility. Using BPTF-null MEFs we show that BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress, but not for c-MYC-driven apoptosis. Consistently, BPTF is required for the proliferation of cells driven by c-MYC, such as Burkitt lymphoma, and its expression in human cancer lines correlates with the activation of c-MYC gene signatures. Our findings point to the c-MYC-BPTF axis as a potential therapeutic target in cancer. To assess whether BPTF is required for the transcriptional activity of c-MYC, human foreskin fibroblasts (HFF) were stably transduced with the chimeric MYC-ER cDNA (HFF MYC-ER) and infected with lentiviruses coding for either control (shNt) or BPTF-targeting shRNAs. Cells were serum-starved for 2 days to achieve quiescence and then treated with 4-hydroxytamoxifen (4-OHT)

ORGANISM(S): Homo sapiens  

SUBMITTER: Enrique Carrillo de Santa Pau   Víctor J Sánchez-Arévalo Lobo  Laia Richart  Enrique Carrillode Santa Pau  F X Real 

PROVIDER: E-GEOD-65544 | ArrayExpress | 2016-01-19

SECONDARY ACCESSION(S): GSE65544SRP053097PRJNA274339

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

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

Richart Laia L   Carrillo-de Santa Pau Enrique E   Río-Machín Ana A   de Andrés Mónica P MP   Cigudosa Juan C JC   Lobo Víctor J Sánchez-Arévalo VJS   Real Francisco X FX  

Nature communications 20160105


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 chromati  ...[more]

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