Journal article
Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity
MW Coolen, C Stirzaker, JZ Song, AL Statham, Z Kassir, CS Moreno, AN Young, V Varma, TP Speed, M Cowley, P Lacaze, W Kaplan, MD Robinson, SJ Clark
Nature Cell Biology | NATURE PUBLISHING GROUP | Published : 2010
DOI: 10.1038/ncb2023
Abstract
Silencing of individual genes can occur by genetic and epigenetic processes during carcinogenesis, but the underlying mechanisms remain unclear. By creating an integrated prostate cancer epigenome map using tiling arrays, we show that contiguous regions of gene suppression commonly occur through long-range epigenetic silencing (LRES). We identified 47 LRES regions in prostate cancer, typically spanning about 2Mb and harbouring approximately 12 genes, with a prevalence of tumour suppressor and miRNA genes. Our data reveal that LRES is associated with regional histone deacetylation combined with subdomains of different epigenetic remodelling patterns, which include re-enforcement, gain or exch..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank K. Patterson, P. Molloy and T. Hulf for reviewing the manuscript. We thank the Ramaciotti Centre, University of NSW (Sydney, Australia) for array hybridizations. This work is supported by Cancer Institute NSW (CINSW) program (S. J. C.), CINSW Fellowship (M. W. C.) and CINSW Student (A. L. S.) grants and National Health and Medical Research Council (NH&MRC) project (427614, 481347) and Fellowship grants (S. J. C. and T. S.) and NBCF program grant.