Distal regulatory elements in cancer progression and treatment: focus on DNA methylation and hydroxymethylation

Projektinformationen

methDRE

ID Finanzhilfevereinbarung: 334013

Abgeschlossenes Projekt

Startdatum 15 November 2013

Enddatum 14 November 2017

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 100 000,00

EU-Beitrag € 100 000,00

Koordiniert durch

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Ziel

In carcinogenesis epigenetic aberrations occur early, are widespread across the genome and are potentially reversible. DNA methylation (5mC) at gene promoters and CpG islands (CGIs) is well recognized for affecting gene expression. In contrast, little is known on the role of DNA methylation in distal regulatory elements (DREs). Based on recent genome-wide studies, we hypothesize that DREs are more sensitive than CGIs to changes in DNA methylation, thus they may function as primary responders to epigenetic therapies. We previously showed DREs are indeed epigenetically dynamic and prone to demethylation, the process that may involve a newly identified DNA modification, cytosine hydroxymethylation (5hmC). The molecular mechanisms by which these modifications are targeted to specific genomic locations are not well understood.
The project aims to identify the role DNA methylation and hydroxymethylation play in the maintenance and functioning of DREs during cancer progression and treatment. For that, genome-wide methods will be developed for the identification of DREs followed by targeted enrichment using DNA capture array and sequencing. This will allow for simultaneous analysis of 5mC and 5hmC modifications at base-pair resolution. We will examine the effects of virus infection and chronic inflammation on DNA methylation and hydroxymethylation in cultured oral keratinoctes while focusing on the changes in transcription factor binding as a potential targeting mechanism. The effect of DNA methylation inhibitors will be examined to identify key methylation events within DREs required for cancer cell survival. Clinical relevance of the key methylated regions will then be evaluated on a panel of head and neck cancers from well characterized cohorts of patients.
This investigation will reveal important molecular aspects of chromatin function in tumorigenesis, thereby improving prospects for developing personalized cancer therapies that target epigenetic modifications.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › microbiology › virology
• natural sciences › biological sciences › genetics › DNA
• medical and health sciences › clinical medicine › oncology › head and neck cancer
• natural sciences › biological sciences › genetics › genomes
• natural sciences › biological sciences › genetics › epigenetics

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2012-CIG
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-CIG - Support for training and career development of researcher (CIG)

Koordinator

THE UNIVERSITY OF BIRMINGHAM

Kontakt Verwaltung

May Chung (Ms.)

• EU-Beitrag: € 100 000,00
• Adresse: Edgbaston ; B15 2TT Birmingham ; Vereinigtes Königreich
• Region: West Midlands (England) › West Midlands › Birmingham
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: Keine Daten