Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.

ABSTRACT: MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference 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 cMAF, 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 enh

SUBMITTER: Rahmat M 

PROVIDER: S-EPMC11649448 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature