Your browser doesn't support javascript.
loading
Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations.
Taberlay, Phillippa C; Achinger-Kawecka, Joanna; Lun, Aaron T L; Buske, Fabian A; Sabir, Kenneth; Gould, Cathryn M; Zotenko, Elena; Bert, Saul A; Giles, Katherine A; Bauer, Denis C; Smyth, Gordon K; Stirzaker, Clare; O'Donoghue, Sean I; Clark, Susan J.
Afiliação
  • Taberlay PC; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia;
  • Achinger-Kawecka J; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia;
  • Lun AT; Bioinformatics Division, Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;
  • Buske FA; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  • Sabir K; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  • Gould CM; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  • Zotenko E; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia;
  • Bert SA; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  • Giles KA; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  • Bauer DC; CSIRO, North Ryde, New South Wales 2113, Australia;
  • Smyth GK; Bioinformatics Division, Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia; Department of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3010, Australia.
  • Stirzaker C; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia;
  • O'Donoghue SI; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; CSIRO, North Ryde, New South Wales 2113, Australia;
  • Clark SJ; Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia;
Genome Res ; 26(6): 719-31, 2016 06.
Article em En | MEDLINE | ID: mdl-27053337
ABSTRACT
A three-dimensional chromatin state underpins the structural and functional basis of the genome by bringing regulatory elements and genes into close spatial proximity to ensure proper, cell-type-specific gene expression profiles. Here, we performed Hi-C chromosome conformation capture sequencing to investigate how three-dimensional chromatin organization is disrupted in the context of copy-number variation, long-range epigenetic remodeling, and atypical gene expression programs in prostate cancer. We find that cancer cells retain the ability to segment their genomes into megabase-sized topologically associated domains (TADs); however, these domains are generally smaller due to establishment of additional domain boundaries. Interestingly, a large proportion of the new cancer-specific domain boundaries occur at regions that display copy-number variation. Notably, a common deletion on 17p13.1 in prostate cancer spanning the TP53 tumor suppressor locus results in bifurcation of a single TAD into two distinct smaller TADs. Change in domain structure is also accompanied by novel cancer-specific chromatin interactions within the TADs that are enriched at regulatory elements such as enhancers, promoters, and insulators, and associated with alterations in gene expression. We also show that differential chromatin interactions across regulatory regions occur within long-range epigenetically activated or silenced regions of concordant gene activation or repression in prostate cancer. Finally, we present a novel visualization tool that enables integrated exploration of Hi-C interaction data, the transcriptome, and epigenome. This study provides new insights into the relationship between long-range epigenetic and genomic dysregulation and changes in higher-order chromatin interactions in cancer.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Epigênese Genética / Neoplasias Limite: Humans Idioma: En Revista: Genome Res Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Epigênese Genética / Neoplasias Limite: Humans Idioma: En Revista: Genome Res Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2016 Tipo de documento: Article