Context
Our body contains more than 400 different types of cells, such as blood cells, skin cells or neurons. Remarkably, these different types of cells share the same genomic information, our DNA, yet they are able to execute completely different functions. This is possible because during development, cells acquire distinct “cell identity”. Cell identity therefore relies on an information called epigenetics that is not contained in our DNA but is instead imposed during development. The aim of IDRE was to understand how the epigenetic information is established and duplicated in dividing cells. It is a fundamental question in biology as failure to safeguard cell identity can lead to diseases such as neurological disorders and cancers. Epigenetics is also an exciting area of research as epigenetic mechanisms can regulate adaptations during the life of an organism, such as lifestyle changes (e.g. diet) or prolonged exposure to environmental chemicals.
Our key findings are:
• We found that when cells duplicate, the duplication of the genomic information is uncoupled from the duplication of the epigenetic information. Moreover, we uncover the role of other DNA based processes in the duplication of the epigenetic information (DOI: 10.1016/j.celrep.2023.111996 DOI: 10.1038/s44319-024-00085-x).
• We have published a resource to reveal how thousands of proteins reassociate with newly replicated DNA in a human finite cell line and in cancer cells. Researchers can easily examine the profile of their protein of interest using our comprehensive datasets in open access (DOI: 10.1016/j.celrep.2023.111996).
• The protein FAM111A is found mutated in a rare human developmental disease, the Kenny Caffey syndrome, but its function remains to be fully understood. Using patient mutations, we have explored the role of FAM111A in the duplication of the genome and uncover a new role for FAM111A in the initiation of this process (DOI: 10.26508/lsa.202302111).
• We have established our technologies to study the maintenance of epigenetic information in human induce pluripotent stem cells and built an atlas of proteins that may safeguard the genetic and epigenetic information in these dividing cells. Human induced pluripotent stem cells are widely used for disease modelling despite a limited understanding of the epigenetic mechanisms established during the reprogramming process. Our work exposes the proteins involved in these processes (in preparation).
Deliverables and next step
Taken together, our data alter our current simplistic models for the duplication of the epigenetic information in unanticipated ways and built the foundation of our next research endeavours. Moreover, I anticipate that this work on fundamental research will fuel translational research. Indeed, the epigenetic factors we have identified are often deregulated in human cancer and intellectual disabilities.
