CHAMELEON
Cellular Hypoxia Alters DNA MEthylation through Loss of Epigenome OxidatioN
| Coordinatore | VIB
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Belgium [BE] |
| Totale costo | 1˙920˙000 € |
| EC contributo | 1˙920˙000 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2013-CoG |
| Funding Scheme | ERC-CG |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-09-01 - 2019-08-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
VIB
Organization address
address: Rijvisschestraat 120 contact info |
BE (ZWIJNAARDE - GENT) | hostInstitution | 1˙920˙000.00 |
| 2 |
VIB
Organization address
address: Rijvisschestraat 120 contact info |
BE (ZWIJNAARDE - GENT) | hostInstitution | 1˙920˙000.00 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (Objective)
'DNA methylation was originally described in the 1970s as an epigenetic mark involved in transcriptional silencing, but the existence of DNA demethylation and the enzymes involved in this process were only recently discovered. In particular, it was established that TET hydroxylases catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) through a reaction requiring oxygen (O2) and 2-oxoglutarate (2OG). DNA demethylation as mediated by TET hydroxylases has so far predominantly been studied in the context of stem cells, but its precise contribution to carcinogenesis remains largely enigmatic. Nevertheless, somatic mutations in TETs have been identified in numerous cancers.
Tumor hypoxia is linked to increased malignancy, poor prognosis and resistance to cancer therapies. In this proposal, we aim to assess how hypoxia directly impacts on the cancer epigenome through the dependence of TET-mediated DNA demethylation on O2. First of all, we will study the effect of O2 and 2OG concentration on TET hydroxylase activity, as well as the overall and locus-specific changes of their product (5hmC). Secondly, because much of the hypoxic response is executed through HIFs, we will investigate how HIF binding is influenced by DNA methylation and if so, whether TET hydroxylases are targeted to HIF (or other) binding sites to maintain them transcriptionally active. Thirdly, we will assess to what extent 5hmC profiles differ between tumor types and construct a comprehensive panel of (tumor-specific) 5hmC sites to assess the global and locus-specific relevance of 5hmC in various cancers. Finally, since hypoxia is a key regulator of the cancer stem cell (CSC) niche and within the tumor microenvironment also promotes metastasis, we will establish the in vivo relevance of DNA demethylation, as imposed by tumor hypoxia, in the CSC niche and during metastasis. Overall, we thus aim to establish the interplay between tumor hypoxia and the DNA methylome.'
Altri progetti dello stesso programma (FP7-IDEAS-ERC)
DEATHSWITCHING (2013)
Identifying genes and pathways that drive molecular switches and back-up mechanisms between apoptosis and autophagy
Read More