Current challenges in understanding the role of enhancers in disease

Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing evidence that enhancer dysfunction due to genetic, structural or epigenetic mechanisms contributes to a broad range of human diseases referred to as enhanceropathies. Such mechanisms often underlie the susceptibility to common diseases, but can also play a direct causal role in cancer or Mendelian diseases. Despite the recent gain of insights into enhancer biology and function, we still have a limited ability to predict how enhancer dysfunction impacts gene expression. Here we discuss the major challenges that need to be overcome when studying the role of enhancers in disease etiology and highlight opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies.

Automated summary

Enhancers are crucial for the spatiotemporal control of gene expression and are cell-type-specific. They are suggested to contribute to phenotypic variation, evolution, and disease. Dysfunction of enhancers, caused by genetic, structural, or epigenetic mechanisms, has been linked to a broad range of human diseases, known as enhanceropathies. Understanding how enhancer dysfunction affects gene expression remains a challenge.