Quantitative dissection of transcriptional control system: N-dependent antitermination complex of phage λ as regulatory paradigm

Abstract

Publisher Summary This chapter discusses that all living organisms depend on precise regulation of complex patterns of gene transcription. Remarkably, the same basic transcriptional machinery is responsible for producing the immense diversity of RNA transcripts at a variety of defined levels. Therefore, in order to satisfy the requirement for specific and timely gene expression, it is necessary for this machinery to be sensitive to an abundance of regulatory mechanisms. As a means of directing spatial and temporal specificity, transcription factors frequently require the assistance of additional protein or nucleic acid components, all of which assemble along with the transcription factor into a transcriptional regulatory complex. The dependence of a transcription factor on cis-acting nucleic acid components directs the sequence specificity of this regulation, and dependence on trans-acting protein components can control the timing and intensity of a regulatory response. The chapter uses basic kinetic and thermodynamic principles to discuss how a transcription complex can achieve a state that is sensitive to regulation. It presents a working model for the assembly of a specific regulatory complex. The method involves addressing quantitatively the individual contributions of accessory factors and defining them as “layers of specificity.” Finally, to provide a set of concrete illustrations of these principles, it describes physicochemical and molecular biological studies of the mechanisms whereby the N protein-dependent antitermination system activates the delayed early genes of bacteriophage λ.