The temporal and spatial expression of specific genes is central to processes such as development, differentiation and homeostasis in eukaryotes, and is regulated primarily at the level of transcription. An understanding of the molecular basis for this regulation has presented a major challenge for the past 40 years. After early insights into genetic control mechanisms in prokaryotes, elegantly elaborated in the classic 1961 paper of Jacob and Monod, it was anticipated by many that similar principles would apply in eukaryotes. However, early studies in animal cells faced the problem of genomic complexity (including reiterated DNA sequences) and the lack of tractable genetic approaches. By the time I entered graduate school in the mid 1960s, the general RNA classes—ribosomal (rRNA), transfer (tRNA), messenger (mRNA) and the enigmatic heterogeneous nuclear (hnRNA)—had been recognized, and variations in the levels of these RNA classes were being defined during various growth, developmental, hormonal and viral responses. However, except for the early work from the laboratories of Max Birnstiel and Don Brown on the purification and structural analysis of the amplified rRNA