Details

Autor(en) / Beteiligte

• Herz, Hans-Martin

Titel

Enhancer deregulation in cancer and other diseases

Ist Teil von

• BioEssays, 2016-10, Vol.38 (10), p.1003-1015

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Mutations in enhancer‐associated chromatin‐modifying components and genomic alterations in non‐coding regions of the genome occur frequently in cancer, and other diseases pointing to the importance of enhancer fidelity to ensure proper tissue homeostasis. In this review, I will use specific examples to discuss how mutations in chromatin‐modifying factors might affect enhancer activity of disease‐relevant genes. I will then consider direct evidence from single nucleotide polymorphisms, small insertions, or deletions but also larger genomic rearrangements such as duplications, deletions, translocations, and inversions of specific enhancers to demonstrate how they have the ability to impact enhancer activity of disease genes including oncogenes and tumor suppressor genes. Considering that the scientific community only fairly recently has begun to focus its attention on “enhancer malfunction” in disease, I propose that multiple new enhancer‐regulated and disease‐relevant processes will be uncovered in the near future that will constitute the mechanistic basis for novel therapeutic avenues. Enhancer deregulation underlies various diseases. It can be caused by mutations in enhancer‐associated chromatin‐modifying factors such as UTX/KDM6A, MLL3/KMT2C, and MLL4/KMT2D or alternatively by mutations or genomic alterations of disease, or cancer gene enhancers. Both cases result in altered enhancer activity of disease‐relevant genes such as tumor suppressor or oncogenes.