Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer
| Autor: | Bernhart, S. (Stephan H), Kretzmer, H. (Helene), Holdt, L. (Lesca M), Juehling, F. (Frank), Ammerpohl, O. (Ole), Bergmann, A. (Anke K), Northoff, B. (Bernd H), Doose, G. (Gero), Siebert, R. (Reiner), Stadler, P. (Peter F), Hoffmann, S. (Steve) |
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| Přispěvatelé: | Leipzig University, Ludwig-Maximilians-Universität München (LMU), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Christian-Albrechts University of Kiel, University of Ulm (UUlm), University of Vienna [Vienna], Max Planck Institute for Mathematics in the Sciences (MPI-MiS), Max-Planck-Gesellschaft, Santa Fe Institute, univOAK, Archive ouverte, Universität Leipzig, Ludwig-Maximilians-Universität, Inserm, U110 - Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Christian-Albrechts-Universität, Universität Ulm, Universität Wien, Max-Planck-Institut für Mathematik in den Naturwissenschaften, Nature Publishing Group |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Aucun
Sciences du Vivant [q-bio]/Médecine humaine et pathologie Article Epigenesis Genetic Cancer epigenetics Neoplasms Humans genetics Genes Developmental Promoter Regions Genetic pathology [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology Chromatin Krebs Gene Expression Regulation Developmental DNA Methylation Chromatin Neoplasm Proteins Gene Expression Regulation Neoplastic Histone Code Next-generation sequencing Data integration CpG Islands ddc:601 bivalent chromatin cancer [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Transcription Factors |
| Zdroj: | Scientific Reports Scientific Reports, 2016, 6 (1), ⟨10.1038/srep37393⟩ Scientific reports 6:37393 Doi: 10.1038/srep37393 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep37393 |
| Popis: | Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin. Tested on over 7,000 DNA methylation data sets from several cancer types, it reaches an AUC of 0.92. Although higher levels of DNA methylation are often associated with transcriptional silencing, counter-intuitive positive statistical dependencies between DNA methylation and expression levels have been recently reported for two cancer types. Here, we re-analyze combined expression and DNA methylation data sets, comprising over 5,000 samples, and demonstrate that the conjunction of hypermethylation of bivalent chromatin and up-regulation of the corresponding genes is a general phenomenon in cancer. This up-regulation affects many developmental genes and transcription factors, including dozens of homeobox genes and other genes implicated in cancer. Thus, we reason that the disturbance of bivalent chromatin may be intimately linked to tumorigenesis. journal article research support, non-u.s. gov't 2016 11 23 2016 11 23 imported |
| Databáze: | OpenAIRE |
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