ENHREG

Exploring enhancers’ Achilles Heel

 Coordinatore STICHTING HET NEDERLANDS KANKER INSTITUUT 

Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.

 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 2˙176˙840 €
 EC contributo 2˙176˙840 €
 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-2012-ADG_20120314
 Funding Scheme ERC-AG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-10-01   -   2018-09-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Dr.
Nome: Henri
Cognome: Van Luenen
Email: send email
Telefono: 31205122097
Fax: +31 20 669 1383

NL (AMSTERDAM) hostInstitution 2˙176˙840.00
2    STICHTING HET NEDERLANDS KANKER INSTITUUT

 Organization address address: PLESMANLAAN 121
city: AMSTERDAM
postcode: 1066 CX

contact info
Titolo: Prof.
Nome: Reuven
Cognome: Agami
Email: send email
Telefono: 31205122079
Fax: 31206691383

NL (AMSTERDAM) hostInstitution 2˙176˙840.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

remote    rnas    ernas    function    erna    binding    coding    enhancer    genes    located    cancer    oncogenic    enhancers       domains    chromatin    cellular    rnapii    interestingly    dependent    transcriptional    regions    transcription    gene   

 Obiettivo del progetto (Objective)

'Enhancers are genomic domains that regulate transcription of distantly located genes and that are characterized by specific chromatin signatures of histone methylation and acetylation patterns. Interestingly, RNA polymerase II (RNAPII) binds to a subset of enhancers and produces transcripts, called enhancer RNAs (eRNAs). These are produced bi-directionally and, in contrast to mRNAs and many other non-coding RNAs, are not polyadenylated. Generally, the transcription of eRNAs was shown to positively correlate with mRNA levels of surrounding protein-coding genes. However, it is unclear if eRNAs carry a transcriptional function.

p53 is a transcription factor and tumor suppressor that is very frequently mutated in cancer. Chromatin-binding profiles reveal specific interactions of p53 with promoter regions of nearby genes, within genes, but also with remote regions located more than 50 kbps away from any known gene. Interestingly, many of these remote regions possess evolutionary highly conserved p53-binding sites and all known hallmarks of enhancer regions, as well as binding of RNAPII. We found out that many remote p53-bound domains are indeed p53-dependent eRNA-producing enhancers, and, most importantly, eRNA production was required for transcriptional induction of distal genes and for p53-dependent cellular control.

Here we will: 1. Investigate in detail the mechanism of action and function of p53-dependent eRNAs. 2. Expand studies to identify eRNAs with oncogenic function. 3. Develop efficient ways to target eRNAs. 4. Target eRNAs and study their capacity to inhibit tumorigenicity.

As eRNAs are mediators of enhancer activity with sequence specific content and sensitivity to siRNA targeting, they might be the Achilles heel through which oncogenic enhancer activity could be suppressed. Our study will elucidate a novel layer of gene regulation and holds promise for opening up new opportunities to affect cancer-related cellular programs in very specific and effectiv'

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