Mahshid Rahmat, Kendell Clement, Jean-Baptiste Alberge, Romanos Sklavenitis-Pistofidis, Rohan Kodgule, Charles P Fulco, Daniel Heilpern-Mallory, Katarina Nilsson, David Dorfman, Jesse M Engreitz, Gad Getz, Luca Pinello, Russell Ryan, Irene M Ghobrial
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引用次数: 0
Abstract
MYC deregulation occurs in the majority of multiple myeloma (MM) cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of MM patients, but it is known to be driven by translocation or amplification events in only ~40% of myelomas. Here, we used CRISPR interference (CRISPRi) to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type specific enhancer leads to increased MYC expression. This native enhancer activity was not associated with enhancer hijacking events but led to specific binding of c-MAF, IRF4, and SPIB transcription factors that activated MYC expression in the absence of known genetic aberrations. In addition, focal amplification was another mechanism of activation of this enhancer in approximately 3.4% of MM patients. Together, these findings define an epigenetic mechanism of MYC deregulation in MM beyond known translocations or amplifications and point to the importance of non-coding regulatory elements and their associated transcription factor networks as drivers of MM progression.
期刊介绍:
The Journal of Chemical Health and Safety focuses on news, information, and ideas relating to issues and advances in chemical health and safety. The Journal of Chemical Health and Safety covers up-to-the minute, in-depth views of safety issues ranging from OSHA and EPA regulations to the safe handling of hazardous waste, from the latest innovations in effective chemical hygiene practices to the courts'' most recent rulings on safety-related lawsuits. The Journal of Chemical Health and Safety presents real-world information that health, safety and environmental professionals and others responsible for the safety of their workplaces can put to use right away, identifying potential and developing safety concerns before they do real harm.