How do genomes encode developmental time?

We have summarized different mechanisms for the temporal control of gene expression based on properties of genome organization. Differences in gene length, enhancer proximity, or tethering element interactions can create temporal differences in gene activity in response to shared activators and regulatory networks. The mechanisms we summarized are probably the tip of the iceberg, and it is easy to anticipate additional features of genome organization that influence the timing of gene activity. This is anticipated by a number of studies suggesting that acute depletion of CTCF leads to a loss of TAD organization without obvious changes in gene expression (e.g., Ghavi-Helm et al. 2019; Hsieh et al. 2022). However, the methods used to measure these changes lack the precision made possible by the use of quantitative live-imaging methods and high-resolution Micro-C assays. It seems likely that TADs and TAD boundaries will prove to be important for the temporal precision of animal development.