The “epigenome” refers to the heritable chemical changes to DNA and histone proteins that can be passed on through cell division and potentially across generations. Dramatic reprogramming of the epigenome begins at conception and continues throughout embryonic and post-natal development, underlying the gene expression changes that drive the generation of diverse cell types that make up complex multicellular organisms. We study how the epigenetic state of mammals is initially established in early development, by exploring transcription factors that recognize parasitic mobile DNA elements to initiate stable heterochromatic silencing. We also study how one large family of these parasitic elements, the endogenous retroviruses or ERVs, play an important role in development and evolution of new traits in mammals by rewiring gene expression networks. Finally, we explore how the epigenetic state of a cell works in conjunction with combinatorial codes of transcription factors to generate the huge diversity of cell types required for mammalian development.