Chapter  10:  Regulation of Transcription Initiation

An active region of transcription producing a “puff” in a Drosophila polytene chromosome. Chromosomes were stained with fluorescently labeled antibodies against the heat shock transcription factor (red) and RNA polymerase II (green). Regions of overlap appear yellow. The transcription factor is concentrated near the 5 end of the transcription unit comprising the puff and at additional positions along the polytene chromosomes. [Photograph courtesy of John R. Weeks and Arno L. Greenleaf.]

One of the underlying principles of molecular cell biology is that the actions and properties of each cell type are determined by the proteins it contains. But what determines the types and amounts of the various proteins that characterize a particular cell type? Or that allow a single-celled organism to respond to changes in its environment? The determining factors are the concentration of each protein’s corresponding mRNA, the frequency at which the mRNA is translated, and the stability of the protein itself. The concentration of various mRNAs is, in turn, determined largely by which genes are transcribed and their rate of transcription in a particular cell type. Thus the differential transcription of different genes largely determines the actions and properties of cells.

The term gene expression commonly refers to the entire process whereby the information encoded in a particular gene is decoded into a particular protein. Theoretically, regulation at any one of the various steps in this process could lead to differential gene expression in different cell types or developmental stages or in response to external conditions. Synthesis of mRNA requires that an RNA polymerase initiate transcription, polymerize ribonucleoside triphosphates complementary to the DNA coding strand, and then terminate transcription (see Figure 4-15). In prokaryotes, ribosomes and translation-initiation factors have immediate access to newly formed RNA transcripts, which function as mRNA without further modification. In eukaryotes, the initial RNA transcript is processed by addition of a poly(A) tail and splicing, which removes noncoding introns, yielding a functional mRNA (see Figure 4-19). The mRNA then is transported from its site of synthesis in the nucleus to the cytoplasm where translation occurs. Finally, the stability of an mRNA affects its concentration in both prokaryotic and eukaryotic cells.

Although examples of regulation at each of the steps in gene expression have been found, control of transcription initiation—the first step—is the most important mechanism for determining whether or not most genes are expressed and how much of the encoded mRNAs, and consequently proteins, are produced. In this chapter, we review current understanding of the molecular events that determine when transcription is initiated. Chapter 11 considers other regulatory mechanisms that control the subsequent steps in gene expression. Chapter 14 presents an overview of how these multiple levels of gene control contribute to the development of specific types of cells in multicellular organisms.