Our genome is like a library full of books, with the books being the genes. Every cell in our body has the same library but need to read different books to fulfill its function. IN addition, cells need to read new books or close the ones already reads in response to external stimuli. Thus, controlled gene expression is a pre-requisite for all cellular processes and an essential determinant of cellular identity. In turn, aberrant gene expression is a hallmark of multifactorial diseases that arise on the background of complex genome-environment interactions. Such genome-environment interactions frequently activate epigenetic mechanisms that add an additional layer of control to the genome and provide cells with a mechanism by which transient stimuli can be transformed into long-term adaptive changes. With reference of our example that the genome is a library and the books are the genes, the epigenetic marks can be viewed as bookmarks in the genome. Key examples of such epigenetic bookmarks are methylation and acetylation of histone-proteins that control the availability of DNA for gene-expression. The addition and removal of these moieties is mediated by the counteracting activity of enzymes that either write or erase these epigenetic marks, the so-called writer and eraser proteins, while epigenetic readers translate the “epigenetic code” into cellular function. In addition, there is increasing evidence that non-coding RNAs control gene-expression and act as key regulators of cellular homeostasis. The role of epigenetic regulation in the adult brain is only emerging but recent evidence suggests that targeting the epigenome could be a suitable novel approach for the treatment of neuropsychiatric and neurodegenerative diseases. A prime example is Alzheimer’s disease which causes a huge emotional and economic burden to our societies and for which no cure is currently available. To better understand the epigenetic underpinnings of brain function in health and disease can help to develop novel approaches for stratified therapies against such devastating diseases. During the course of DEPICODE, we could make substantial progress in this direction.
