INTEGER · Integrated approaches to study gene regulation during cellular differentiation

Cellular differentiation from stem cells to fully functional mature cells is a multi step process executed by complex transcription programs. Once differentiated, cells must faithfully maintain their identity through cellular memory mechanisms. The utilisation of genetic information stored in linear DNA sequence occurs within the three dimensional context of chromatin, chromosomes and the nucleus, all of which contribute to gene regulation mechanisms. The main aim of this ITN is to get a comprehensive view on the mechanisms controling gene expression during cell differentiation by integrating studies on multiple regulatory levels from DNA binding transcription factors through to nuclear organization. We will take a multi-faceted approach addressing the functions of: (i) transcription factors and their co-factors (ii) chromatin domains and histone variants, (iii) epigenetic mechanisms of cellular memory and identity, (iv) global gene interactions in nuclear space and (iv) nuclear territories of gene activity. Genomics approaches will be employed to describe global changes in gene target networks and gene interactions in the nucleus during ES cell differentiation into the hepatic, neuronal and hematopoietic lineages. Proteomics will be employed for the characterization of transcription factor and epigenetic modifying complexes and of the in vivo protein composition of specialized chromatin domains. The research activities of this ITN are organized in the context of a multidisciplinary Training Program, which provides unique opportunities for the training of early stage researchers to address fundamental biological questions with far reaching implications in biotechnology and human health.