We show that in addition to promoter activation, MYC drives cancer progression by activating transcriptional enhancers via a distinct mechanism. MYC cooperates with several other proteins at these cis-regulatory regions to change the epigenome and promote recruitment of RNA polymerase II and enhancer transcription.
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References
Baluapuri, A., Wolf, E. & Eilers, M. Target gene-independent functions of MYC oncoproteins. Nat. Rev. Mol. Cell Biol. 21, 255–267 (2020). A review article that describes the transcriptional mechanisms underlying MYC function.
Lin, C. Y. et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151, 56–67 (2012). This paper reports MYC enhancer invasion upon overexpression.
Papachristou, E. K. et al. A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes. Nat. Commun. 9, 2311 (2018). This paper describes the qPLEX-RIME method to study protein interactomes.
Kalkat, M. et al. MYC protein interactome profiling reveals functionally distinct regions that cooperate to drive tumorigenesis. Mol. Cell 72, 836–848 (2018). This paper reports the interactomes of full-length MYC and various MYC mutants.
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This is a summary of: Jakobsen, S. T. et al. MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch. Nat. Genet. https://doi.org/10.1038/s41588-024-01676-z (2024).
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MYC activates transcriptional enhancers to drive cancer progression. Nat Genet 56, 567–568 (2024). https://doi.org/10.1038/s41588-024-01677-y
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DOI: https://doi.org/10.1038/s41588-024-01677-y
