118646 Journal Article.pdf (1.37 MB)
Alterations in three-dimensional organization of the cancer genome and epigenome
journal contribution
posted on 2023-05-19, 07:40 authored by Achinger-Kawecka, J, Phillippa TaberlayPhillippa Taberlay, Clark, SJThe 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.
Funding
National Health & Medical Research Council
History
Publication title
Cold Spring Harbor Symposia on Quantitative BiologyVolume
81Pagination
41-51ISSN
0091-7451Department/School
Tasmanian School of MedicinePublisher
Cold Spring Harbor Lab PressPlace of publication
Publications Dept, 500 Sunnyside Blvd, Woodbury, USA, Ny, 11797-2924Rights statement
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.Repository Status
- Open