Consolidation of the cancer genome into domains of repressive chromatin by long-range epigenetic silencing (LRES) reduces transcriptional plasticity
Marcel W Coolen, Clare Stirzaker, Jenny Z Song, Aaron L Statham, Zena Kassir, Carlos S Moreno, Andrew N Young, Vijay Varma, Terence P Speed, Mark Cowley, Paul Lacaze, Warren Kaplan, Mark D Robinson, Susan J Clark
NATURE CELL BIOLOGY | NATURE PUBLISHING GROUP | Published : 2010
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 2 Mb 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 exc..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NATIONAL CANCER INSTITUTE
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.