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Mechanisms underlying epigenetic regulation by small non coding RNAs

For a long time it has been accepted that a big part of the genome consisted of the so-called ''junk'' DNA without functional importance. Through the ENCODE project it has been evident that the vast majority of this DNA is in fact... ver más

Fecha desconocida

ETH Zürich

275K€

Presupuesto del proyecto: 275K€

Líder del proyecto

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto No tenemos la información de la convocatoria

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ETH Zürich

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Líder del proyecto

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 275K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto For a long time it has been accepted that a big part of the genome consisted of the so-called ''junk'' DNA without functional importance. Through the ENCODE project it has been evident that the vast majority of this DNA is in fact transcribed into RNA, producing a huge number of small and long non-coding RNAs (ncRNAs) of unknown function. Previous studies suggested that ncRNAs may be implicated among others in epigenetic regulation. Aim of the current project is to investigate the mechanisms underlying this form of regulation with regards to gene silencing by Polycomb Repression Complex 2 (PRC2) and establishment of specific chromatin marks like H4K12 acetylation. As a model system we employ mouse pluripotent stem cells during differentiation and reprogramming, which are characterized by remarkable chromatin remodelling offering the possibility to track chromatin dynamics in relation with changes in ncRNAs. We will apply RIP-seq for PRC2 to identify small ncRNAs associated with action of this complex and test how they are connected with silencing of selected genomic regions in our model system. To this end, we want to identify the mechanisms through which these ncRNAs guide PRC2. In addition, we want to develop a high throughput approach to map genome wide at the chromatin level small ncRNAs associated with selected histone modifications like H4K12 acetylation and check their distribution around critical genomic elements like promoters and splice junctions. Deliverables of this project will provide an unprecedented insight into the way chromatin modifications and complexes are involved in epigenetic regulation via ncRNAs. This project combines the field of epigenetics with the emerging field of ncRNAs. It will enable the applicant to interact with a lab in Harvard which is world leader in the field of ncRNAs and a lab in ETH Zurich which is driving force in epigenetics, thus creating interesting synergies between the two research environments towards RNAepigenetics.

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