DNAMETHYLOOPMCL
Of DNA methylation and looping of distant regulatory elements in mantle cell lymphoma
| Coordinatore | CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Organization address
address: CALLE ROSSELLO 149 PUERTA BJS contact info |
| Nazionalità Coordinatore | Spain [ES] |
| Totale costo | 166˙336 € |
| EC contributo | 166˙336 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2012-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-02-01 - 2016-05-22 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Organization address
address: CALLE ROSSELLO 149 PUERTA BJS contact info |
ES (BARCELONA) | coordinator | 166˙336.20 |
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Obiettivo del progetto (Objective)
'B-cell differentiation is a complex process in which epigenetic changes, i.e., DNA methylation and histone modifications, play an essential role to regulate gene expression. Disturbances in epigenetic processes can result in development of B-cell malignancies, such as mantle cell lymphoma (MCL). So far, little is known about the epigenetic alterations underlying MCL. In general, epigenetic studies in cancer have mainly dealt with identification of hypermethylated promoter regions. Recent genome-wide studies in B cell malignancies however, have shown that the majority of DNA methylation changes do not occur in promoter regions but at intra- and intergenic loci, which are enriched for enhancers. In this project, I wish to study the functional impact of DNA methylation changes at these enhancer regions on DNA looping and gene expression regulation in MCL. To achieve this goal, I will generate genome-wide chromosome conformation maps of MCL and normal naive B cells using Hi-C sequencing. Additionally, I will generate DNA methylation profiles, histone modification maps and gene expression profiles of these samples. Combining these datasets will allow identification of intra- and intergenic enhancer regions that, based on differences in DNA methylation status, affect DNA looping and gene expression. The effect of DNA methylation on enhancer activity of these regions will then be studied in further detail using luciferase reporter assays. The proposed study shall give insights into (i) the effect of DNA methylation outside promoter regions on DNA looping and gene expression (fundamental aspect); (ii) the DNA methylation changes in MCL that affect these processes (biological aspect); and (iii) the functional impact of differential DNA methylation between MCL subtypes (clinical aspect). The latter 2 shall lead to better understanding of the underlying molecular mechanisms of MCL and may form a basis to design new therapeutic strategies for this aggressive disease.'