| First Author | Signaroldi E | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10753 | PubMed ID | 26923714 |
| Mgi Jnum | J:234827 | Mgi Id | MGI:5790922 |
| Doi | 10.1038/ncomms10753 | Citation | Signaroldi E, et al. (2016) Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network. Nat Commun 7:10753 |
| abstractText | 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. |
