Before we turn our attention to the regulation of gene expression in eukaryotes, consider for a moment the expression of constitutive, or housekeeping, genes that are always active. The requirement that some genes are always “on” raises questions about cellular priorities of gene expression. Constitutive gene products are sets of many polypeptides that form large macromolecular complexes in cells, or enzyme sets that participate in vital biochemical pathways. How do cells maintain such polypeptides in stoichiometrically reasonable amounts? Or, can their levels rise or fall transiently without much effect? Recent studies suggest that transcription of housekeeping genes is in fact, not at all coordinated! Nevertheless, we also saw that the efficiency of glycolysis relied on the evolution of allosteric regulatory mechanisms to control the activities of glycolytic enzymes rather than their transcription. While this takes care some element of metabolic control, a problem remains. Recall that protein synthesis is energy-intensive, each peptide linkage costing three NTPs (not to mention the waste of an additional NTP per phosphodiester linkage made in transcription of an mRNA!). The overproduction of proteins under any circumstances would seem to be a waste of energy. We may not know just how expensive it is to express housekeeping genes. But whatever they are, these energy expenses are the cost of evolving complex structures and biochemical pathways vital to their everyday function and survival. Now back to our focus on regulated gene expression… in eukaryotes.