The differentiation of cells and tissues during development is governed by distinct spatiotemporal transcriptional programmes. As part of ENCODE 3, He, Williams and co-workers1 have generated bulk transcriptome data across 12 tissues at various timepoints between embryonic day 10.5 (E10.5) and E16.5, and for 17 tissues at birth (P0). Principal component analysis (PCA) and other clustering approaches showed that tissues clustering according to their developmental origins, with transcriptomes of developing haematopoietic and neuronal tissues polarizing towards opposite ends. Three classes of temporal drivers of developmental change were found: universal drivers across all tissues (for example, mitotic cell cycle components), cell-type-specific differentiation drivers (for tissues such as skeletal muscle) and regulators of inter-tissue cell migration. Global RNA co-expression patterns were intersected with frequencies of transcription factor (TF) motifs, revealing gene clusters that are likely to be transcriptionally co-regulated. Cluster-specific putative regulatory mechanisms were explored by integrating the co-expression data with epigenomic datasets. For better cellular resolution, forelimb tissue developmental stages were subjected to single-cell RNA sequencing, identifying 25 distinct cell types over the course of development from limb bud (E10.5) to forelimb (E15). Using bulk histone modification, chromatin accessibility, DNA methylation data and limb DNAse peak calls from accompanying studies, candidate regulatory elements were annotated for all tissues, and for the limb, they were further parsed to cell types and states. While these annotations still require experimental confirmation at the cell type and state levels, these data allow researchers to infer tissue developmental trajectories of gene regulation.