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CANCER EPIGENETICS

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Comprehensive characterization of epigentic reprogramming in cancer

Epigenetics refers to heritable changes in gene expression patterns, brought about by modifications to DNA and chromatin. Aberrant epigenetic activity was shown to play important roles in the tumorigenic process. Two major epigene... ver más

29/02/2012

Sheba Research Fun...

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT A... No se ha especificado una descripción o un objeto social para esta compañía.

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-02-29 No tenemos la información de la convocatoria

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2 Participantes

Sheba Research Fund

100.00K€ | Lider

MEDICAL RESEARCH INFRASTRUCT...

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Líder del proyecto

MEDICAL RESEARCH INFRASTRUCTURE DEVELOPMENT A... No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Epigenetics refers to heritable changes in gene expression patterns, brought about by modifications to DNA and chromatin. Aberrant epigenetic activity was shown to play important roles in the tumorigenic process. Two major epigenetic systems are known: DNA methylation and the histone modification machinery, an important component of which is the Polycomb Repressive Complexes (PRC) system. Recent works have suggested that a link between the two systems exists in cancer cells. Previous work on the interaction between DNA methylation and PRC activity was mostly limited to studies of a small number of genes leading to partial and conflicting results. I propose a long term comprehensive study that aims to examine the correlated epigenetic changes in these systems occurring through the spectrum of the tumorigenic process. This is made possible by a new methodology we have developed involving simultaneous genome-wide profiling of DNA methylation and PRC activity followed by robust computational analysis of the data. This gives us a unique ability to probe correlated changes of the various epigenetic systems. The project will be based on an established lab-computational-biotech collaboration and will entail simultaneous genome-wide profiling of epigenetic systems in normal and cancer cells and in various stages of the immortalization/transformation process. Results of the initial phase of this study show significant interplay between the two epigenetic systems. In particular, it appears that the two silencing mechanisms act in parallel to reprogram the cancer epigenome, and that DNA hypermethylation may replace Polycomb based repression near key regulatory genes, possibly reducing their regulatory flexibility. I expect the project to lead to a characterization of the gradual evolution of epigenetic states during the tumorigenic process, and their contribution to the transformation of normal cells to cancer cells.

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