Publisher Summary This chapter provides the theories of transcriptional regulation in eukaryotic cells. Current ideas about the mechanisms involved in differentiation have been very much influenced by the studies on the regulation of protein synthesis both in prokaryotes and eukaryotes. It is now clearly recognized that in mammalian cells the same basic rules as in bacteria that probably apply in the genetic information for protein synthesis is included in DNA; this is transcribed to messenger RNA, and this in turn is translated into protein by a machinery involving ribosomes, activating enzymes, transfer RNA, and other factors. In eukaryotic cells there may be additional mechanisms not identified in prokaryotes. The chromosomes are much more complex and are segregated from the cytoplasm in the cell nucleus. The evidence that transcriptional controls play an important role in differentiation comes mainly from the studies using the technique of RNA/ DNA hybridization. Labeled RNA is hybridized rapidly from a variety of mouse tissues to DNA in competition with the samples of unlabeled RNA from the same tissues. These studies indicated the differences in RNA populations from one tissue to another.