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Content archived on 2024-05-29

The role of bHLH-LZ transcription factors on epigenetic programming during cell proliferation and differentiation

Objective

How epigenetic programming of promoter architecture compatible with cell fate decisions is established and maintained is not well understood. We will explore the concept that during the cell cycle or on gene silencing, the bHLH-LZ transcription factor USF is a critical determinant of promoter architecture by mediating the transient and targeted recruitment of chromatin organisers to genes targeted by the master regulator of melanocyte development the bHLH-LZ factor Mitf, and that USF thereby dictates the ability of Mitf to control melanocyte stem cell and melanoma proliferation/differentiation.

The specific aims are:
1. To determine promoter occupancy by USF and Mitf at key target genes during the cell cycle and on gene activation/repression.
2. To identify protein complexes through which USF mediates its effects on gene regulation.
3. To examine the role of USF in melanocyte stem cell proliferation and differentiation.

The results will reveal both general principles underlying gene regulation and the mechanisms of epigenetic re-programming necessary for lineage commitment. The proposal addresses important but poorly understood issues in cell fate determination with long term implications for stem cell therapy and USF-associated diseases such as hyperlipidemia and diabetes. Moreover the project extends the researcher and apos;s current interests and will provide high quality and apos;state-of-the-art and apos; technical and intellectual training that will equip him to fulfil his long term ambition for an independent research career in France. The project will also foster close collaboration and technology transfer between the host UK laboratory and the researcher and apos;s current group in France and enhance and extend a current informal and synergistic network of European laboratories working in this field.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2005-MOBILITY-5
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

MARIE CURIE CANCER CARE (RESEARCH INSTITUTE)
EU contribution
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Total cost

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