Eukaryotic gene transcription

GENETWORK

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£d/tor Adrian Bird, Institute for Cell and Molecular Biology at the University of Edinburgh

BOOKS Reading the blueprint Eukaryodc Gene Transcription edited by Stephen Goodbourn IRL Press,1996.£29.50pbk 012 pages)ISBN0 19 9634866 Since its beginnings in the early 1960s with the experiments of Jacob, Monnd and others, the gene regulation field has become perhaps the largest and most intensely active area of biological research. This expansion reflects the fact that many key regulators that were discovered in areas of research such as developmental biology, cell-cycle regulation and cancer biology tamed out to be transcription factors or other transcription components. Thus, the study of transcriptional regulation embraces parts of these fields as well. Given this complexity it is not surprising that even transcription experts, to say nothing of students or investigators in different fields, have difficulty keeping

up with the pace of developments. This is addressed, to some extent, by the regular appearance of transcriptional regulation review atxicles in journals such as Trends in Genetics and elsewhere. However, there is definitely a place for a more lengthy discussion of recent advances and the direction of current research. In Eukaryotic Gene Transcription Stephen Goodboum has brought together a series of essays designed to do just this while also reviewing the underlying principles of transcriptional control. The first chapter concentrates on RNA polymerase II basal transcription machinery and the mechanism by which transcriptional activators are believed to TIG APmL 1997 VOL. 13 No. 4

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work. Pol I and Pol II1 promoters also receive a brief mention. An important feature that has emerged from studies of Pol I1 transcription is the complexity of the basal transcription machinery. Transcriptional activation or, for that matter, repression by sequence-specific transcription factors, involves direct or indirect protein-protein interactions between transcription factors and various components of the basal transcription machinery. Targets for protein-protein interaction include the general transcription factors TFIIB, TFIIE, TFIIF, TFIIH and components of the multisubunit WIID, including the TATA-box-binding factor TBP. The precise string of events that leads from interaction with one or more of these target molecules to modulation of transcription is often unclear. But a point that is made in the book is that many components of the basal machinery are targets for different activators and at least in some cases, for example the strong activator VP16, protein-protein contacts are made with

B O O K S

multiple components of the basal machinery, presumably allowing synergistic action. The transcriptional reguhtion paradigm above derives mostly from in vitro experiments, and ignores the effect of nucleosomes and higher--order chromatin structure on transcription. Transcription in t,ivo, of course, occurs in the context of chromatin within a structured nucleus. This fact is at least partially addressed in the chapter by Man Wolfe entitled Histones

and Transcriptional Control. The remainder of the book consists of seven essays each covering an area where significant recent advances have been made and illuminating different aspects of transcriptional regulation. Each of these chapters begins with a sensible amount of background information, goes on to illuminate current understanding in the field and ends with suggestions of future directions. The introduction to each chapter

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is fairly extensive. Chapter 3, for example, which describes the CREM transcription factor family and its role in transcriptional responses to the second messenger cAMP, contains a general discussion of transcription factor organization and structure, and goes on to desctibe bZ1P transcription factors in some detail before focusing in on the main subject material. It is ob~,iously impossible in a book of this size to review the entire transcriptional regulation field comprehensively (a recent Cold Spring Harbor Monograph entitled Transcriptional Regulation mn to over 1300 pages) but the book does succeed in covering many topical areas and gives a good perspective. However, no book is perfect and an area that receives little coverage is the role of higher-order chromatin organization and epigenetic regulation of transcription. Specifically, enhancer and locus-controlregion function, position effect, epigenetic

"~ What you pay is what you get GeneJockey II v2.0 for Apple Macintosh (CD-ROH) BIOSOFT,1996.£500.00(software),£1000.00(softwareplusdatabaseupdates) The WebGenetics Sequence Analysis Server URL htt.p:llwww.webgenetics.coml TQSoft For most European laboratory biologists, sequence analysis functions are now readily available through the services of EMBnet. Nevertheless, many would still like to analyse sequences on personal computers in their own laboratory. BioSoft's GeneJockeypackage aims at this market. The software comes on CD-ROM with a full set of darabases, and an extensive manual. Installing the GeneJocko, program was simple and painless. The manual is a very readable introduction to the functions available, and users should take the trouble to read it despite the author's assertion that many users 'will probably never need the manual anyway'. The manual ctmtains a series of 16 tutorials explaining the basics of the Genelockey functions, with step-by-step instructions and the required background information on the methods used. Naturally, in a low-priced package for a personal computer, there are some catches. Several of the functions turn out to be fairly ba.~ic compared with those available in the major Unix packages. Many, however, are very comprehensive. The trick i'., to identify which is which. For example, a protein hydropathy plot can .be.tricky for the novice because a bewildering choice of properties can be

plotted. The last tutorial explains in detail how to select a standard analysis, and also what some of the less familiar selections can provide. On the other hand, a novice trying sequence alignment might, unintentionally, choose a very basic alignment method instead of the rigorous gapped alignments. A very welcome feature is the ability to update the data files used by the GeneJockey. The restriction enzyme sites and prosite patterns can be updated using the usual anonymous FTP sites. It is also possible to add new translation tables for those working with organdie sequences. Some data, though, is not expandable. Sadly, this includes the comparison matrices for sequence alignment (PAM100 and PAM250 are provided, and are fine for most purposes, but for example there is no BLOSUM matrix) Overall, GeneJockeyrepresents reasonable value compared with the prices of the more complete personal computer packages, and the package is certainly moving in the right direction, but it cannot replace access to a full featured sequence analysis package (e.g. LaserGene, http:// www.dnastar.confflasergen/lasergen.hmO. As biologists begin to make use of the World Wide Web, sites are beginning to appear which offer sequence analysis T I G APRIL 1997 VOL. 13 N o . 4

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control of transcription through Polycomb-group genes and parental imprinting are current hot topics that might have been included. But, to be fair, these are all subjects that are discussed at length in a previous book in the series edited by Sarah Elgin entitled Cbromatin

Structure and Gene Expression. To summarize, this book reports on a number of key areas in transcriptional regulation. It is well referenced and clearly wdnen, and should be accessible to a readership including undergraduate students, while also helping those already working in the field to keep abreast of recent developments. l a n G. C o w e l l [email protected]

Department of Biochemistryand Genetics, Universityof Neg~:astle,Newcastleupon Tyne, UK NE24HH.

functions over the Web. WebGeneticsis apparently a commercial server, run by a company called TQSofi. However, the pages give no clue to who TQSOfl are, or where they are based. The WebGeneticsserver offers a menu of standard sequence analysis options. Each has its own help page, and most standard functions are covered. Sequences are sent by cot and paste, or can be loaded through the Web browser. Trying the programs, though, is a big disappointment. The protein hydrophobicity plot offers something called 'Kyte&Doodle' (sic), which rams out to be Kyte and Doolittle parameters divided by 1.5 because the program can only handle values of +3 to -3. Other analyses, such as those in GeneJockey, are available but usually fail to plot. Secondary structure prediction also has incorrect citations, has help pages from the original program instead of the Web version, and is far poorer titan other methods (e.g. PHD the protein structure prediction server at http://www.embl-beidelberg.de/ predictprotein/and DSC - discrimination of protein secondary structure class at http://www .icnet.uk/bmm/dsc/dsc form _align.html) freely available over the Web. Homology searching is even worse. Although the sequence databases in WebGenetics are up to date, the searches simply point to NCBI's pages. Verdict: most Web servers are worth checking from time to time as they improve rapidly. WebGenetics, in its present state, is not worth visiting. -

P e t e r Rice [email protected]

hlformatics Division, 1be SangerCentre, WellcomeTrustGenomeCampus, Hinxton, Cambridge, t~" CBIOISA.