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Trends Genet. 2019 Feb;35(2):145-158. doi: 10.1016/j.tig.2018.11.007. Epub 2018 Dec 18.

Chromatin Interactions and Regulatory Elements in Cancer: From Bench to Bedside.

Author information

1
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore; These authors made equal and critical contributions.
2
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore. Electronic address: mfullwood@ntu.edu.sg.

Abstract

Chromatin interactions regulate gene expression by bringing distal regulatory elements, such as super-enhancers, to promoters in close spatial proximity. It has been recognized that in cancer, chromatin interactions can be dysregulated, leading to aberrant oncogene expression. Chromatin interactions may potentially serve as biomarkers, or be modulated via CRISPR therapy and small molecule inhibitors against transcription. However, these methods face challenges that must be resolved and raise questions for further research. Understanding chromatin interactions is essential for safety aspects of anticancer therapies, such as the mechanism of action of epigenetic regulators and transcription factors in cancer, and potential off-target effects arising from targeting super-enhancers and promoters. In this review article, we discuss how chromatin interactions and regulatory elements may become dysregulated in cancer, potential methods to target them for clinical therapy, and outline outstanding questions that require addressing before epigenetic therapies can translate to the clinic safely and effectively.

KEYWORDS:

cancer; chromatin interaction; enhancer; therapy

PMID:
30577989
DOI:
10.1016/j.tig.2018.11.007

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