MYC intragenic distal regulatory element (MYC-DRE)

The MYC intragenic distal regulatory element is a critical non-coding DNA sequence that functions as an enhancer to regulate the transcription of the MYC proto-oncogene. Although located far from the MYC promoter—often within the gene body of the neighboring PVT1 long non-coding RNA gene or within the 3' region of the MYC locus—it physically interacts with the MYC promoter through long-range chromatin looping [4, 8]. This element is characterized by epigenetic marks of active enhancers, such as H3K27 acetylation, and is frequently hijacked or amplified in various malignancies, including breast and colorectal cancers, to drive oncogenic MYC overexpression [9, 13]. In these disease states, the enhancer recruits transcriptional co-activators like BRD4 and the Mediator complex to stimulate high levels of MYC mRNA production [12]. Because MYC itself is notoriously difficult to target with small molecules, this regulatory element has emerged as a high-priority therapeutic target [7]. Current experimental strategies include the use of CRISPR-based epigenome editing to silence the enhancer and small-molecule BET inhibitors to disrupt its interaction with the MYC promoter [15, 21]. However, therapeutic intervention must be carefully managed due to MYC's essential role in normal cellular processes like hematopoiesis and intestinal regeneration.

Other names

PVT1 intragenic enhancerMYC distal enhancer8q24 enhancer clusterMYC 3' Wnt-responsive element (WRE)MYC-associated distal regulatory element

Inhibition of MYC transcription by disrupting enhancer-promoter loops or preventing the recruitment of transcriptional co-activators to the regulatory site.