Stranger than fiction: Epigenetics (Novartis Foundation Symposium 214) edited by D.J. Chadwick and G. Cardew

Abstract

John Wiley & Sons, 1997. £57.50 hbk (305 pages)ISBN 0 471 97771 3This volume, from a Novartis (formerly Ciba) Foundation Symposium on Epigenetics conceived by Alan Wolffe, is a densely packed, well-presented and fascinating survey. The volume comprises (in addition to Wolffe's introduction and summary) 16 chapters recording presentations from various research groups, five general discussions and a comprehensive index. Subjects include a variety of ‘epigenetic favourites’ from yeast, flies, plants and mammals, including: DNA methylation and associated proteins; Polycomb and trithorax group genes; globin LCR function; yeast mating type, centromeres and Sir proteins; mammalian X chromosome inactivation and genomic imprinting; transposon regulation; and much more. As such, coverage of this enormous field is surprisingly comprehensive. This is partly because the generous page allocations to post-chapter discussions and lists of cited references results in more effective coverage than suggested by perusal of the volume contents page. Additionally, several of the research presentations and much of the discussion attempts to integrate mechanistic features from different systems and, although the extent to which this is achieved is variable, many of the resulting discussions are illuminating.I particularly enjoyed T.H. Bestor's proposal that (in addition to its role in imprinting) the function of mammalian DNA methylation is primarily that of a suppressor of ‘parasitic DNA’, rather than as a developmental or tissue- specific regulator of gene activity. This proposal successfully integrates recent molecular genetic studies in the mouse and human with arguments based on phylogenetic comparisons and, indeed, a companion chapter (by M.A. Matzke and A.J.M. Matzke) on transgene silencing in plants proffers a related argument. If the basic idea is not entirely new, it has certainly not previously been presented as forcefully, and it seems to me that these articles represent a watershed in our understanding. Of course, the volume contains many other sections of equal interest, however, presumably due to space restrictions, not all receive equitable treatment; for example, histone acetylation is rather sparsely covered.It would be pointless to attempt to summarize further the varied topics addressed in this volume, although Wolffe makes a fair attempt in seven pages of combined introduction and final summary. What comes across is the sense of epigenetics as a rather loosely defined area of enormous complexity, interest and opportunity. Moreover, browsing the text, there is almost the sense of epigenetic strangeness, in that, until relatively recently, many of the mechanisms described here might not have looked out of place in science fiction. Certainly, non-translatable RNA has arrived as a significant factor in gene regulation. Perhaps there is a reminder here: that the expectation of widespread conservation of important themes and mechanisms of gene regulation across the phylogenetic spectrum, which is founded to some extent on certain constraints that must operate in protein evolution, may be irrelevant in the RNA world. Are RNA-based mechanisms of gene regulation likely to be less conserved and therefore stranger? I don't know. Buy the book.