Whole-body regeneration, i.e., the capacity to replace any missing cell type lost to injury, is observed in many metazoan lineages. How molecular and genetic pathways launched upon wounding promote regeneration is poorly understood, and little is known about how these pathways compare across animal phyla. We utilize the highly regenerative acoel worm Hofstenia miamia, which represents the sister-lineage to all other bilaterians, as a laboratory model to uncover mechanisms for regeneration. We generated a high-quality genome sequence assembly and applied epigenomic profiling over the course of regeneration in Hofstenia to identify dynamically changing chromatin. Studies of these loci revealed binding sites and cognate transcription factors that mediate early stages of regeneration. Specifically, by combining functional assays with chromatin profiling, we inferred a gene regulatory network (GRN) that is launched upon amputation in Hofstenia. We are using this GRN as a substrate for comparing regeneration across distantly related animal lineage as several components of this GRN are upregulated upon injury in planarians, sea stars, and cnidarians. Furthermore, we are leveraging the abundant and accessible embryos of Hofstenia to develop new tools for mechanistic studies of regeneration. The embryos of Hofstenia also provide an opportunity to study the evolution of many defining features of the bilaterian body plan and to identify the developmental origins of neoblasts, the population of pluripotent stem cells that underlies the regenerative capacity of acoels.