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Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome

Citation

Achinger-Kawecka, J and Taberlay, PC and Clark, SJ, Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome, Cold Spring Harbor Laboratory Symposia on Quantitative Biology, 81 pp. 41-51. ISSN 0091-7451 (2016) [Refereed Article]


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Copyright 2016 Achinger-Kawecka et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted reuse and redistribution provided that the original author and source are credited.

DOI: doi:10.1101/sqb.2016.81.031013

Abstract

The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome. Notably, we find that additional topologically associated domain (TAD) boundaries are formed in cancer cells resulting in smaller TADs and altered gene expression profiles. The new TAD boundaries are commonly associated with copy-number changes observed in the cancer genome. We also identified new cancer-specific chromatin loops within TADs that are enriched for enhancers and promoters. Finally, we find that many of the long-range epigenetically silenced (LRES) and long-range epigenetically active (LREA) regions in cancer are characterized by differential chromatin interactions. Together our data provide a new insight into charting alterations in higher-order structure and the relationship with genetic, epigenetic, and transcriptional changes across the cancer genome.

Item Details

Item Type:Refereed Article
Keywords:chromatin, nucleosome, three-dimensional, cancer
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. Genome Methylation and Epigenomics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Taberlay, PC (Dr Phillippa Taberlay)
ID Code:118646
Year Published:2016
Funding Support:National Health and Medical Research Council (1109696)
Deposited By:Medicine (Discipline)
Deposited On:2017-07-17
Last Modified:2017-09-18
Downloads:7 View Download Statistics

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