The study of gene regulation has rapidly advanced by leveraging next-generation sequencing to identify and characterize the cis and trans elements that are critical for defining cell identity. These advances have paralleled a movement towards whole genome sequencing in clinics. These two tracks have increasingly synergized to underscore the importance of cis-regulatory elements in development as well produce countless studies implicating these elements in human disease. Other studies have emphasized the clinical phenotypes associated with variation or mutations in trans factors, including non-coding RNAs and chromatin regulators. These studies highlight the importance of obtaining a comprehensive understanding of mammalian gene regulation for predicting the impact of genetic variation on patient phenotypes. Currently lagging behind the generation of vast datasets and annotations is our ability to examine these putative elements in the dynamic context of a developing organism.