Epigenetic changes play important roles in cancer, metabolic and aging-related diseases, but also during loss of resilience as they cause the genetic material to be incorrectly interpreted in affected cells. A major study by scientists at Helmholtz Munich published in ’Nature’ now provides important new insights into how complex epigenetic modification signatures regulate the genome. This study will pave the way for new treatments of diseases caused by faulty epigenetic machineries.