Detection and Employment of Biological Sequence Motifs

Background

The concept of motifs and their relationship to regulation of the cellular environment can be traced back to the late 1950s. Although regulatory elements had been shown to exist in DNA as early as 1951 (McClintock, 1951), it was the work of Jacques Monod and Francois Jacob regarding the regulation of lactose metabolism in Escherichia coli that lead to the first generalized theory concerning regulatory elements. Via the lac repressor, a protein which moderates the translation of the proteins used in lactose synthesis, Jacob et al. were able to develop a framework accounting for transcriptional regulation (Jacob, Perrin, Sanchez, and Monod, 1960). This seminal work only considered repressor elements and was primitive in comparison to modern views regarding transcriptional regulation; however, it is notable in that it presents the concept of an operator, a segment of DNA to which regulatory elements may bind.

At about the same time, a number of motifs were being identified within gene promoter regions. Promoters are DNA sequences which regulate the initiation of transcription of nearby genes. The 1970s saw the discovery of two conserved motifs that recruit the general transcriptional factors and RNA polymerase (Hurwitz, 1960; Stephens, 1960) to promoters: the TATA box “TATAA” (Rifton, Goldberg, Karp, & Hogness, 1978) and the Pribnow box “TATAAT” (Pribnow, 1975). The former is called the Goldberg-Hogness Box in eukaryotes, and the latter is known as the -10 sequence in bacterial promoters.Additional promoter motifs have since been identified and underscore the regulatory complexity between prokaryotes and eukaryotes. Bacterial promoters usually have three unique motifs while eukaryotic promoters can have up to seven (Clancy, 2008).