Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network
| Autor: | Arianna Brancaccio, Elisa Reisoli, Giuseppe Testa, Paolo Malatesta, Maria Rosa Terreni, Sina Atashpaz, E. Signaroldi, Silvia Cristofanon, Pasquale Laise, Claudio Doglioni, Giancarlo Pruneri |
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| Přispěvatelé: | Signaroldi, Elena, Laise, Pasquale, Cristofanon, Silvia, Brancaccio, Arianna, Reisoli, Elisa, Atashpaz, Sina, Terreni Maria, Rosa, Doglioni, Claudio, Pruneri, Giancarlo, Malatesta, Paolo, Testa, Giuseppe |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cells Science Inbred Strains Down-Regulation Polycomb-Group Proteins General Physics and Astronomy Mice Inbred Strains SMAD macromolecular substances Biology Article General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Promoter Regions Histones Mice 03 medical and health sciences Genetic Polycomb-group proteins Animals Humans Gene silencing Gene Silencing Promoter Regions Genetic Transcription factor Cells Cultured Epigenomics Epigenesis Genetics Regulation of gene expression Neoplastic Cultured Multidisciplinary Base Sequence Female Gene Expression Regulation Neoplastic Glioma Protein Binding Transcription Factors fungi General Chemistry Cell biology 030104 developmental biology Gene Expression Regulation Epigenetic Repression |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Malignant gliomas constitute one of the most significant areas of unmet medical need, owing to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We find that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated with invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a critical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signalling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signalling. Polycomb-mediated gene regulation has been implicated in gliomas. Here the authors integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, and find that the Polycomb-dependent silencing of the transcription factor Zfp423 hinders survival. |
| Databáze: | OpenAIRE |
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