Synthetic Epigenetics

Genetically identical cells can exhibit distinct gene expression and phenotypic states that persist through cell division, a capability that is fundamental to the processes of environmental adaptation, cellular differentiation and multicellular development. These heritable states, which do not involve changes in DNA sequence, are maintained and transmitted by self-propagating epigenetic mechanisms. In this talk, I will share my lab’s recent efforts to use synthetic biology to explore and manipulate two different epigenetic systems. First, I will describe the construction of an orthogonal regulatory system in mammalian cells, based on synthetic factors that can “write” and “read” a rare DNA modification. We have used this system to predictively engineer epigenetic functions in order to study basic principles of chromatin-based epigenetic control and to encode additional layers of epigenetic information in cells. Second, I will describe how we are using synthetic biology to illuminate an altogether different form of epigenetic information, encoded in the self-perpetuating conformations of yeast prion proteins, and to exploit them as the basis of engineering synthetic cellular memories.