DNA decoding is evolving beyond gene identification to the more complex challenge of understanding regulatory elements, a “blue ocean” field following breakthroughs like AlphaFold. To decipher the elusive coding rules of promoters, Associate Professor Hsin-Hung Chou’s team at National Taiwan University utilized high-throughput synthesis to analyze millions of E. coli promoters, establishing a massive database to train a computer model for analyzing 49 bacterial genomes. Their systems biology approach led to two major discoveries: the identification of a previously unrecognized, conserved “Start” region that marks the mRNA initiation site—similar to elements in Archaea and Eukaryotes, suggesting a common evolutionary ancestor—and a distinction in the “Discriminator” region between Terrabacteria and Gracilicutesthat dictates growth-dependent gene expression. Featured as the cover story in Nucleic Acids Research (Vol. 53, No. 21), this study offers significant insights into the evolutionary conservation of gene regulation mechanisms.