TY - JOUR
T1 - Current challenges in understanding the role of enhancers in disease
AU - Zaugg, Judith Barbara
AU - Sahlén, Pelin
AU - Andersson, Robin
AU - Alberich-Jorda, Meritxell
AU - de Laat, Wouter
AU - Deplancke, Bart
AU - Ferrer, Jorge
AU - Mandrup, Susanne
AU - Natoli, Gioacchino
AU - Plewczynski, Dariusz
AU - Rada-Iglesias, Alvaro
AU - Spicuglia, Salvatore
N1 - © 2022. Springer Nature America, Inc.
PY - 2022/12/8
Y1 - 2022/12/8
N2 - 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.
AB - 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.
U2 - 10.1038/s41594-022-00896-3
DO - 10.1038/s41594-022-00896-3
M3 - Book/Film/Article review
C2 - 36482255
SN - 1545-9993
JO - Nature Structural & Molecular Biology
JF - Nature Structural & Molecular Biology
ER -