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TCF4 transcriptional program in crypt stem cells and resulting differentiated cells

Project information

Grant agreement ID: 221108

Status

Closed project

  • Start date

    1 March 2008

  • End date

    28 February 2010

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 227 373,86

  • EU contribution

    € 227 373,86

Coordinated by:

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands

Objective

The Wnt pathway is a key regulatory pathway in development and carcinogenesis. Many of the components of the pathway connecting Wnt to the transcription factor TCF4 have been identified. However, our knowledge of the regulation of TCF4 promoter and enhancer elements in response to the Wnt signal, resulting in development from a stem cell to a differentiated cell, is limited. Largely due to technical constrains it has not been possible to identify TCF4 bound DNA enhancer elements or protein complexes associated with them which dictate specificity of the Wnt signal in the developing tissue. The mouse intestinal epithelium is a rapidly renewing tissue under the control of the canonical Wnt pathway, and therefore ideal to study the above mentioned questions. The proposed project combines state of the art ChIP on chip Genome wide Agilent DNA arrays, Mass Spectrometry, Flow Cytometry, as well as conventional Biochemistry and Molecular Biology to examine Wnt/TCF4 controlled intestinal development in mice. Using these techniques I will identify distal TCF4 regulatory elements, the associated promoters and the protein complexes responsible. Study of the associated complexes and epigenetic marks will help to identify mechanism of activation and repression of the Wnt pathway resulting in the differentiation from a stem cell to a differentiated cell. Stem cells and their development or the misregulation resulting in tumor growth are of major interest to the academic as well pharmaceutical world for their potential use in treatment (stem cells) or the need for a cure (cancer). Therefore it is important to understand how these processes are regulated in vivo. Research in this ever expanding field is very important to maintain Europe’s scientific excellence in the future.

Coordinator

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Address

Dr Molewaterplein 40
3015 Gd Rotterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

Administrative Contact

Riet Van Zeijl (Ms.)

Participants (1)

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW

Netherlands

EU Contribution

€ 227 373,86

Project information

Grant agreement ID: 221108

Status

Closed project

  • Start date

    1 March 2008

  • End date

    28 February 2010

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 227 373,86

  • EU contribution

    € 227 373,86

Coordinated by:

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands

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