Histone H3 lysine 27 acetylation-marked active enhancer region (H3K27ac-marked enhancer)

H3K27ac-marked epigenetic enhancer regions are distal genomic elements characterized by the acetylation of lysine 27 on histone H3, a modification that serves as a hallmark of active enhancers (Creyghton et al., 2010). These regions are critical for the spatial and temporal regulation of gene expression, distinguishing active enhancers from poised or inactive states and maintaining cell-type-specific identities (Rada-Iglesias et al., 2011). In many diseases, particularly cancer, these regions are hijacked to form large clusters known as super-enhancers that drive the aberrant expression of oncogenes, a phenomenon termed transcriptional addiction (Hnisz et al., 2013). Therapeutic strategies aim to disrupt the maintenance or reading of these marks using inhibitors of BET bromodomain proteins like BRD4, histone acetyltransferases like p300/CBP, or transcriptional kinases like CDK7 (Loven et al., 2013; Lasko et al., 2017; Kwiatkowski et al., 2014). While H3K27ac is a robust biomarker for active regulatory landscapes, it often functions in concert with other epigenetic modifications and transcription factors to coordinate complex gene expression programs. Beyond oncology, these regions are implicated in neurodegenerative conditions such as Alzheimer's disease and various autoimmune disorders, where altered enhancer activity contributes to pathological gene expression (Nativio et al., 2018).

Other names

Active enhancerH3K27ac enhancerSuper-enhancerH3K27ac-enriched regionActive regulatory element

Inhibition of BET bromodomain readers (e.g., BRD4), histone acetyltransferases (e.g., p300/CBP), histone deacetylases (HDACs), or transcriptional kinases (e.g., CDK7/9) to disrupt the assembly and function of active enhancer complexes.