Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing

Hovestadt, V., Jones, D. T., Picelli, S., Wang, W., Kool, M., Northcott, P. A., et al. (2014). Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature, 510(7506), 537-541. doi:10.1038/nature13268.

Item is

Dateien

einblenden: Dateien
ausblenden: Dateien
:
Hovestadt.pdf (Verlagsversion), 7MB
Name:
Hovestadt.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
© 2014 Macmillan Publishers Limited
Lizenz:
-

Externe Referenzen

einblenden:
ausblenden:
externe Referenz:
http://www.ncbi.nlm.nih.gov/pubmed/24847876 (beliebiger Volltext)
Beschreibung:
-
OA-Status:

Urheber

einblenden:
ausblenden:
 Urheber:
Hovestadt, V., Autor
Jones, D. T., Autor
Picelli, S., Autor
Wang, W., Autor
Kool, M., Autor
Northcott, P. A., Autor
Sultan, M.1, Autor           
Stachurski, K., Autor
Ryzhova, M., Autor
Warnatz, H.-J.1, Autor           
Ralser, M., Autor
Brun, S., Autor
Bunt, J., Autor
Jager, N., Autor
Kleinheinz, K., Autor
Erkek, S., Autor
Weber, U. D., Autor
Bartholomae, C. C., Autor
von Kalle, C., Autor
Lawerenz, C., Autor
Eils, J., AutorKoster, J., AutorVersteeg, R., AutorMilde, T., AutorWitt, O., AutorSchmidt, S., AutorWolf, S., AutorPietsch, T., AutorRutkowski, S., AutorScheurlen, W., AutorTaylor, M. D., AutorBrors, B., AutorFelsberg, J., AutorReifenberger, G., AutorBorkhardt, A., AutorLehrach, H.2, Autor           Wechsler-Reya, R. J., AutorEils, R., AutorYaspo, M. L.3, Autor           Landgraf, P., AutorKorshunov, A., AutorZapatka, M., AutorRadlwimmer, B., AutorPfister, S. M., AutorLichter, P., Autor mehr..
Affiliations:
1Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              

Inhalt

einblenden:
ausblenden:
Schlagwörter: Animals Binding Sites Cell Line, Tumor Chromatin/genetics/metabolism Chromatin Immunoprecipitation DNA Methylation/*genetics Female *Gene Expression Regulation, Neoplastic *Gene Silencing Genome/genetics Histones/metabolism Humans Medulloblastoma/*genetics/pathology Mice Promoter Regions, Genetic/genetics RNA-Binding Proteins/genetics Sequence Analysis, DNA/*methods Transcription Factors/metabolism Transcription, Genetic
 Zusammenfassung: Epigenetic alterations, that is, disruption of DNA methylation and chromatin architecture, are now acknowledged as a universal feature of tumorigenesis. Medulloblastoma, a clinically challenging, malignant childhood brain tumour, is no exception. Despite much progress from recent genomics studies, with recurrent changes identified in each of the four distinct tumour subgroups (WNT-pathway-activated, SHH-pathway-activated, and the less-well-characterized Group 3 and Group 4), many cases still lack an obvious genetic driver. Here we present whole-genome bisulphite-sequencing data from thirty-four human and five murine tumours plus eight human and three murine normal controls, augmented with matched whole-genome, RNA and chromatin immunoprecipitation sequencing data. This comprehensive data set allowed us to decipher several features underlying the interplay between the genome, epigenome and transcriptome, and its effects on medulloblastoma pathophysiology. Most notable were highly prevalent regions of hypomethylation correlating with increased gene expression, extending tens of kilobases downstream of transcription start sites. Focal regions of low methylation linked to transcription-factor-binding sites shed light on differential transcriptional networks between subgroups, whereas increased methylation due to re-normalization of repressed chromatin in DNA methylation valleys was positively correlated with gene expression. Large, partially methylated domains affecting up to one-third of the genome showed increased mutation rates and gene silencing in a subgroup-specific fashion. Epigenetic alterations also affected novel medulloblastoma candidate genes (for example, LIN28B), resulting in alternative promoter usage and/or differential messenger RNA/microRNA expression. Analysis of mouse medulloblastoma and precursor-cell methylation demonstrated a somatic origin for many alterations. Our data provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis, which are probably also of importance in a wider developmental and disease context.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2014-05-182014-06-26
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/nature13268
ISSN: 1476-4687 (Electronic)0028-0836 (Print)
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Nature
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: London : Nature Publishing Group
Seiten: - Band / Heft: 510 (7506) Artikelnummer: - Start- / Endseite: 537 - 541 Identifikator: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238