Enhancer Remodeling During Early Mammalian Embryogenesis: Lessons for Somatic Reprogramming, Rejuvenation, and Aging

Abstract

Early during mammalian embryogenesis, epiblast cells undertake major cell fate decisions, becoming specified towards either the perishable soma or the immortal germline. Despite the importance of these developmental transitions, the transcriptional regulatory mechanisms orchestrating them have remained poorly characterized due to the transient nature and scarcity of the involved cell populations. However, our view of these processes is dramatically changing due to advances in mouse and human embryonic stem cell (ESC) differentiation models that faithfully recapitulate peri-implantation transitions. Recent studies using these models have uncovered enhancers as critical cis-regulators during the maintenance, extinction, or re-establishment of pluripotency. Here, we review the major transcriptional and epigenetic regulators controlling the remodeling of enhancer landscapes during mammalian peri-implantation development. Last but not least, we discuss how a global and mechanistic understanding of enhancer remodeling can provide important insights into somatic reprogramming, the molecular basis of aging, and the implementation of cellular rejuvenation strategies.