# Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions

## TL;DR

This paper reviews how DNA methylation at super-enhancers influences cancer by regulating gene activity and offers insights into new cancer therapies.

## Contribution

The paper provides a comprehensive review of the role of DNA methylation in modulating super-enhancer activity and its implications for cancer therapy.

## Key findings

- Dysregulated DNA methylation at super-enhancers affects transcription factor recruitment in cancer.
- Hypomethylation at super-enhancers is linked to oncogene activation in malignancies.
- DNA methylation patterns in super-enhancers serve as potential cancer biomarkers.

## Abstract

The interplay between DNA methylation and super-enhancer activity is emerging as a key focus in cancer research. Super-enhancers, a specialized class of enhancers, strongly activate transcription of their target genes due to their dense clustering with essential transcription factors (TFs) and cofactors. In cancer, especially, these super-enhancers control key oncogenic drivers and often display abnormal DNA methylation patterns that can repress or overexpress target genes in both solid and blood cancers. Furthermore, DNA methylation in the super-enhancer region has been found to influence their regulatory capacity. Although enhancers are typically characterized by low DNA methylation, dysregulated methylation at super-enhancers is seen in most malignancies, affecting TF and chromatin regulator recruitment. Hypomethylation at these sites often accompanies oncogene hyperactivation, while hypermethylation can repress tumor suppressor mechanisms. Recent research highlights DNA methylation as a promising source of cancer biomarkers. This review examines the intricate relationship between DNA methylation and super-enhancer activity in cancer, concentrating on how methylation regulates super-enhancers, modulates oncogene expression, promotes oncogenesis, and serves as a target for novel oncology therapies.