Fundamentals of transcription

Abstract

Genes & Signalsby Mark Ptashne and Alexander Gann,Cold Spring Harbor Laboratory Press, 2002.US$39.00/£28.00 (208 pages) ISBN 0 879 69633 8In the preface, the authors express hope that their book, Genes & Signals, will introduce the general principles of gene control and place them in the larger context of other biological processes. Like most scientists, I spend my time scrutinizing the metaphorical bark of a chosen tree, and so it would be of great benefit for men of vision to show me the forest in which that tree stands. I began to read with enthusiasm.Chapter one introduces transcriptional regulation in Escherichia coli, using clear diagrams and lucid descriptions. Three modes of transcription activation are described. The main focus is on recruitment as a mechanism used by regulatory proteins to control specific genes. For example, the bacterial catabolic activator protein, CAP, induces lac genes by binding RNA polymerase and recruiting it to the promoter. Chapter two explains how recruitment is extensively used in regulation of gene expression in a simple eukaryote, the yeast Saccharomyces. The authors argue that Saccharomyces does not use the other two modes of bacterial regulation described in chapter one, and they conclude that the control of transcription in yeast is based on recruitment. Examples of the more complex transcriptional patterns found in higher eukaryotes are described in chapter three. In each case, the authors assert that regulated recruitment underlies the greater complexity. The final chapter provides further examples of other enzymatic processes that also involve recruitment, such as the Grb2 protein, which binds cell-surface receptors and recruits Son of Sevenless (SOS) to activate signalling cascades. Clearly, recruitment is a recurring theme in biochemistry.But is recruitment a universal theme, as implied by the authors of Genes & Signals? Perhaps. However, Struhl has argued persuasively for a ‘fundamentally different logic of gene regulation in eukaryotes and prokaryotes’ [1xFundamentally different logic of gene regulation in eukaryotes and prokaryotes. Struhl, K. Cell. 1999; 98: 1–4Abstract | Full Text | Full Text PDF | PubMed | Scopus (316)See all References][1]. Many scientists believe that activators in mammals can stimulate post-recruitment steps. Ptashne and Gann do not attempt to refute this; instead they largely ignore it. This made me suspect that their aim might be to persuade readers with the ‘recruitment mantra’, rather than provide a balanced and objective perspective.I was frustrated by the extreme selectivity of the authors’ descriptions. For example, the essential basal factors TFIIB and TFIIF are only mentioned in passing, with nothing said about their nature or role. However, these fundamental components of the transcription apparatus are conserved throughout eukaryotic evolution, and are required for expression of all protein-encoding genes. By contrast, the authors’ favourite activator, Gal4, is discussed dozens of times, although it regulates a mere handful of genes and is only found in fungi. Am I being pedantic here? After all, the authors do not claim to provide an exhaustive description of the transcription machinery. But they are telling us what they consider to be important, so one can legitimately take issue. Even if Ptashne and Gann are not interested in TFIIB, its importance is undeniable and should be made clear in a book of this size. I am very uncomfortable with the idea that readers might get the impression that Gal4 is a central transcription factor and TFIIB a peripheral detail. In fact, the truth is precisely the opposite, although Gal4 has certainly provided a very important paradigm. There are many other examples of imbalance in this book. For example, a salient difference between prokaryotes and higher organisms is that prokaryotes have a single RNA polymerase, whereas eukaryotic nuclei use three. In Genes & Signals, RNA polymerases I and III are mentioned in a single footnote, and yet these essential enzymes are responsible for ∼80% of nuclear transcription. The authors focus exclusively on RNA polymerase II, but what about the other systems? Can one be confident that this book provides a sweeping vision, when most of eukaryotic gene expression is ignored?And the thesis itself? Have Ptashne and Gann taken a step back from the trees and described the bigger picture in its beautiful simplicity? Or is this reductionism ad absurdam, a statement of the obvious fact that molecules must come together to function? I suggest you read the book and decide for yourself: it is quite entertaining. But bear in mind that it advocates a particular viewpoint in the way of a manifesto rather than providing the balanced account that a textbook should provide.