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Molecular mechanisms of retinoid receptor function in pluripotent cells

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Research objectives and content
Retinoids play a fundamental role in regulation of cell proliferation, differentiation and embryonal morphogenesis. Pluripotent embryonal carcinoma (EC) cells differentiate upon retinoic acid (RA) administration and provide a model system to study the RA-regulation of gene expression during early stages of development. Critical for EC cell differentiation is the transactivation of the RARb2 promotervia retinoid receptors (RAR and RXR) binding to RA-responsive elements (RAREs) in close proximity to the TATA-box. I propose to investigate the role of transcription factor TFIIA in RA-dependent signalling pathway through the RARb2 promoter. In the RARb2 promoter TFIIA overlaps with the 3'-RARE. Since binding of the receptor heterodimer to this element is critical for transcriptional activation, it will be important to assess the requirement for TFIIA in RARb2 promoter transactivation. This study will provide insight not only into the role of TFIIA in retinoid dependent signalling in pluripotent cells but also in transcription initiation, in general.
Training content (objective, benefit and expected impact)
The molecular biology/biochemical approach proposed will be beneficial to the applicant's training, at both theoretical and technical levels, as an independent researcher. Training of young researchers from less favoured regions of the community is likely to have a major impact on their scientific development. Upon return, the applicant will both introduce the advanced technologies and promote possible collaborations.
Links with industry/industrial relevance (22)

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Finanzierungsplan

RGI - Research grants (individual fellowships)

Koordinator

Katholieke Universiteit Nijmegen - Stichting Katholieke Universiteit
EU-Beitrag
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Adresse
1,Toernooiveld
6525 ED Nijmegen
Niederlande
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Beteiligte (1)