Final Report Summary - EPIGEPLAS (Epigenetic determinants of the genome that govern cellular plasticity)
Individual cell types are defined by the particular set of genes they express. How does the cell organize the genome to activate the right gene when needed and to keep it silent at other times? This regulation relies on a complex interplay between proteins that bind to regulatory sequences and the packaging of DNA, which can be changed by modifying proteins within nucleosomes (histones) or by methylating the DNA without changing its sequence. These so called epigenetic modifications provide an additional layer of information that in concert with the genetic sequence regulate genome activity. The goal of the ERC project EpiGePlas was to ask how much chromatin and DNA modifications depend on the underlying DNA sequence. Towards this goal the project developed new genomic approaches to measure the epigenome at different cell states and applied genome editing approaches to test how changes in the DNA sequence translate to changes in the epigenome. The project EpiGePlas showed in several high impact publications that DNA methylation and chromatin marks depend highly on the activity of transcription factors. Since these are cell-type specific the chromatin state of regulatory regions is highly variable between cells. These findings explain dynamic chromatin and DNA methylation patterns and link genetic and epigenetic regulatory pathways.