Super-enhancer complex regulating MYC transcription (MYC-SE complex) (MYC-SE complex)

The super-enhancer complex regulating MYC transcription is a large cluster of transcriptional enhancers characterized by high densities of master transcription factors, coactivators, and epigenetic marks like H3K27ac (Hnisz et al., 2013, Nature). These complexes are critical for driving the exceptionally high levels of MYC expression required for the maintenance of the malignant phenotype in various cancers, including multiple myeloma and acute myeloid leukemia (Loven et al., 2013, Cell). Key components of this complex include the bromodomain protein BRD4, the Mediator complex (specifically MED1), and transcriptional kinases such as CDK7 and CDK9 (Kwiatkowski et al., 2014, Nature). Because cancer cells are often "addicted" to the high levels of MYC produced by these super-enhancers, targeting the assembly or activity of this complex has emerged as a potent therapeutic strategy (Bradner et al., 2017, Cell). Small molecule inhibitors, such as BET inhibitors (e.g., Birabresib) and CDK7 inhibitors (e.g., THZ1), work by disrupting the recruitment of transcriptional machinery to these sites, leading to a disproportionate decrease in MYC levels compared to other genes (Ott et al., 2012, Cancer Cell). This selective suppression induces cell cycle arrest and apoptosis in tumor cells while sparing normal cells to a degree, though clinical challenges regarding toxicity and resistance remain (Doroshow et al., 2020, Nature Reviews Clinical Oncology).

Other names

MYC super-enhancerMYC-associated super-enhancerMYC-SESuper-enhancer-driven MYC expression complex

Inhibition of bromodomain-containing proteins (e.g., BRD4) or transcriptional kinases (e.g., CDK7, CDK9) that are essential for the assembly and activity of the super-enhancer complex, thereby selectively suppressing MYC oncogene transcription.