University of Oulu

Xia, J.-H.; Wei, G.-H. Enhancer Dysfunction in 3D Genome and Disease. Cells 2019, 8, 1281.

Enhancer dysfunction in 3D genome and disease

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Author: Xia, Ji-Han1; Wei, Gong-Hong1
Organizations: 1Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2019
Publish Date: 2020-03-23


Spatiotemporal patterns of gene expression depend on enhancer elements and other factors during individual development and disease progression. The rapid progress of high-throughput techniques has led to well-defined enhancer chromatin properties. Various genome-wide methods have revealed a large number of enhancers and the discovery of three-dimensional (3D) genome architecture showing the distant interacting mechanisms of enhancers that loop to target gene promoters. Whole genome sequencing projects directed at cancer have led to the discovery of substantial enhancer dysfunction in misregulating gene expression and in tumor initiation and progression. Results from genome-wide association studies (GWAS) combined with functional genomics analyses have elucidated the functional impacts of many cancer risk-associated variants that are enriched within the enhancer regions of chromatin. Risk variants dysregulate the expression of enhancer variant-associated genes via 3D genomic interactions. Moreover, these enhancer variants often alter the chromatin binding affinity for cancer-relevant transcription factors, which in turn leads to aberrant expression of the genes associated with cancer susceptibility. In this review, we investigate the extent to which these genetic regulatory circuits affect cancer predisposition and how the recent development of genome-editing methods have enabled the determination of the impacts of genomic variation and alteration on cancer phenotype, which will eventually lead to better management plans and treatment responses to human cancer in the clinic.

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Series: Cells
ISSN: 2073-4409
ISSN-E: 2073-4409
ISSN-L: 2073-4409
Volume: 8
Issue: 10
Article number: 1281
DOI: 10.3390/cells8101281
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3122 Cancers
Funding: This work was supported by funding from the Academy of Finland (284618 and 279760); Jane and Aatos Erkko Foundation.
Academy of Finland Grant Number: 284618
Detailed Information: 284618 (Academy of Finland Funding decision)
279760 (Academy of Finland Funding decision)
Copyright information: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (