Abstract
Epigenetic states inherently define a wide range of complex biological phenotypes and processes in development and disease. Accurate cellular modeling would ideally capture the epigenetic complexity of these processes as well as the accompanying molecular changes in chromatin biochemistry including in DNA and histone modifications. Here we highlight recent work that demonstrate how multicellular systems provide a natural approach to capture complex epigenetic phenomena. They accomplish this through more closely matching the in vivo environment and through the intrinsic nature of multicellular systems being able to generate and model multiple distinct cellular states, all within one system. We also discuss challenges and limitations of such systems, efforts to tune and modulate epigenetics directly in multicellular systems, and how molecular interventional approaches could advance and improve the utility of these models.