Chantal Wicky Collaud
The normal development of an organism relies on transcription factors and chromatin modifiers that instruct cells to develop into the various cell and tissue types forming the body. Indeed, complex regulation of cell differentiation does not only depend on transcription regulation, but also on chromatin structure. Chromatin is a very dynamic structure that can be altered by specialized enzymatic complexes, which in turn are modulating gene expression. Our lab chose to investigate the function of these chromatin remodelers during the development of an organism focusing on the following questions: how are chromatin modifyiers driving development? How are epigenetic changes involved in specification of germ and somatic cells? Can we change the fate of a cell by artificially modifying the epigenome?
To pursue this goal, we are using the nematode Caenorhabditis elegans. This tiny little worm presents many advantages for these studies: chromatin factors very similar to human, well characterized development and many useful molecular tools. As an entry point into the regulatory network of chromatin remodelers, we focused our attention on the chromatin modifier Mi2. Two Mi2 homologs are required for proper C elegans development. One of them, LET-418 plays a specific role in postembryonic development. This process involves proliferation and differentiation of the blast/stem cells. We propose that LET-418/Mi2 together with other chromatin factors, are necessary to modulate chromatin structure in order to allow these cells to exit quiescence, to proliferate and to differentiate (Erdelyi et al. 2017). Furthermore, our recent data indicates that the developmental function of LET-418/Mi2 depends on the insulin-signaling pathway.
In the embryo, our recent biochemical and genomic studies have revealed the teamwork of the two Mi2s, LET-418 and CHD-3 in fine-tuning chromatin composition at target genes involved in development (Käser-Pebernard et al. 2016). Our research aims at a better understanding of important epigenetic processes underlying development and stem cell biology.