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~ ] O O K [ E I E V I E W S

Heterochromatin - Molecular and Structural Aspects

edited by Ram S. Verma, Cambridge University Press, 1988. £30.00/$49.50 (xv + 301 pages)

ISBN 0 521 33480 2

Some 60 years ago, Heitz intro- duced the name heterochromatin to describe chromosomal segments or chromosomes that remain con- densed during interphase and stain differently from the mass of nuclear chromatin. Heterochromatin is sometimes associated with interest- ing and unusual genetic and cyto- logical behaviour - for example late or early replication, elimin- ation, cyclical inactivation, hetero- morphism, genetic instability, imprinting and position effects - and might, therefore, hold the key to understanding important aspects of gene control and chromosome evolution.

However, the connection between these extensively docu- mented phenomena and hete- rochromatin itself, about which we know comparatively little, is obscure. This fact is reflected in this multi-author book, fully half of which is devoted to one chapter on the biology of heterochromatin, with selected molecular and struc- tural aspects being described in the remaining eight relatively short chapters. These latter chapters pro- vide up-to-date critical surveys of work on evolutionary aspects of the satellite DNA sequences of heterochromatin in Drosophila, centromeric heterochromatin and kinetochore structure, the three- dimensional structure of hete- rochromatin, and heterochromatin in chromosome banding and poly- morphisms.

Reflecting the heterogeneity of phenomena subsumed under this title, the chapters vary unaw~idably in style and scope, but overall they succeed in reflecting the contem- porary state of this field in a way that is not to be found in any other

single source. The style ranges from that of the pure review, for example of the evolution of Drosophila satellite DNA, to experi- mental and comparatively technical accounts of human chromosome banding as demonstrated by restric- tion enzyme treatment. The former would grace a specialist review journal, while the latter could have found its place in a human chromosome handbook. The 147 page chapter on the biology of heterochromatin by B. John, con- taining 389 references, is by any standards an important critical review of more general interest which, with the inclusion of more introductory and background mat- erial, could stand alone as an authoritative monograph.

A fair appraisal of the field from reading this book is that good progress is being made in under- standing the organization of hetero- chromatin at the level of ultrastruc- ture and DNA sequences. Models are emerging of heterochromatin in terms of chromatin folding and of its involvement in nuclear architec- ture about which there is a measure of general agreement. However, DNA sequence data have not produced the hoped-for insights into the causal mechanisms of heterochromatin and its associat- ed phenomena. As is evident from reading this book, the field is inun- dated with fascinating observations and awash with data from a great variety of different types of study but has yet to focus upon a uni- fying hypothesis. It may therefore be appropriate in the present con- text to summarize my own thoughts about this aspect.

Constitutive heterochromatin, which the book concentrates on, appears on an evolutionary timescale and is regarded as an essentially different phenomenon from facultative heterochromatin, which arises as a consequence of the inactivation of chromatin dur- ing development. However, while acknowledging that both are largely metabolically inert and that they are structurally indistinguish- able, few accounts (including this one) have speculated about a pos- sible common derivation. For some time, however, it has seemed likely to me that both aspects reflect

the same fundamental causal mech- anism.

The model I have suggested, based on observations of the heterochromatin of the sex bivalent, involves mutations in genes whose normal function is to control the hierarchy of processes involved in chromosome conden- sation. These hypothetical mu- tations cause chromosomes, or parts of them, to condense out of phase, either at a particular devel- opmental stage or permanently depending on their individual nature. Most will be lethal, but others obviously are not, for reasons I have outlined else- where.

There is good evidence that the developmental condensation of the inactivated mammalian X chromo- some to form facultative hete- rochromatin is controlled by a sin- gle gene, Xce, which seems likely to be a mutant gene of this type. According to this model, Xce sus- tained a conditional mutation in an ancestral mammal bringing it under the control of a hemizygously expressed X-linked sex gene involved in embryonic differentia- tion. Accordingly, all X chromo- somes except one per genome con- dense and are thereby inactivated. The model ew)kes such a mutation in a similar Y- (or W-) linked gene (Yce), under the control of a somat- ically repressed germ-line sex gene, to explain the permanent somatic (constitutive) heterochromatin of the heterogametic sex chromo- some. Depending upon the extent to which the mutation interferes with its developmental expression and recombination, the chromo- some concerned exhibits facultative heterochromatin (X), or constitutive heterochromatin (Y/W). The latter permits rapid DNA evolution, which, as mentioned in this book, is commonly but as expected from this model not invariably associated with this type of heterochromatin. In principle, similar mechanisms can explain autosomal hetero- chromatin.

If such a model is correct, it sug- gests that in future the critical ques- tions raised in this book may be asked as profitably at the level of the genetic control of hetero- chromatin as at the molecular and

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structural level. Meanwhile, Verma and his contributors are to be con- gratulated in bringing forth a valu- able book that is a timely milestone on the road toward the eventual solution of the heterochromatin problem. As such, it will appeal to advanced students as well as pro- viding a unique reference source

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for researchers in the field. I cer- tainly am very happy to add it to my own collection.

KEN JONES

Institute of A nimal Genetics. University of Edinburgh, West Mains Road, Edinburgh EH9

3J~ UK.

Experiments in Animal Development

by Robert W. Merriam, Sinauer Associates, 1988. $14.95 (i + 101 pages) ISBN 0 87893

525 8

Whether viewed as a nightmare or as an exciting challenge, one of the problems faced by any university teacher of develop- mental biology is to provide prac- tical classes for students whose

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3.5 DAY CHICKEN EMBRYO (FROM EXPERIMENTS IN ANIMAL

I)EVELOPMENT).

schedules permit them to spend no more than three hours at a precisely stated time on a particu- lar day. It is very hard and/or

expensive on materials to be reasonably sure that living embryos at desired stages of development are available to coincide with the time set for the practical class. Most of us remember occasions when the provision of living mat- erial has failed, or when an experi- ment fails for other reasons, and last minute changes of plan have to be made to avoid a complete waste of time on everybody's part.

For these reasons, a textbook providing details of practically orientated work that can profitably occupy students is particularly wel- come. This short, 100-page book contains details of 16 laboratory classes; each of these is intended to occupy students for a period of three hours. Some of the classes

are entirely 'dry', sim- ply involving the analysis of data and the answering of questions on the results presented. Most, however, have some involvement with living material and these will be par- ticularly valuable.

A range of organ- isms is used for these practical classes, including sea urchins, Xenopus, sponges, slime moulds and insect salivary gland giant chromosomes. The practical classes range from rather simple ones such as watching sea urchin fertilization, to rather

complex ones such as analysing the kinds of proteins synthesized. The main manual contains a sub- stantial background description of

the problem and experiment for each practical class. There is then a section on the actual experimental work to be done, a few comments on the kind of report expected from students, and then 3-6 refer- ences concerning the background on which the practical work is based. In the case of the 'dry' practical classes, the description in the manual is considerably exten- ded, to the extent of being an abstract of the originally published work. This will include tables or diagrams. The students are expect- ed to work carefully through the data and then answer five or six questions on the interpretation and understanding of the results presented.

Accompanying the student man- ual is a small booklet entitled 'Instructor's Handbook' . This gives additional notes on each of the 16 practical classes, and includes further comments on the objectives of the experiments, the amount and type of preparation required by the instructor, details of solu- tions required, and (particularly helpfully) ready commercial sources of living material. The Instructor's Handbook also gives answers to the questions that have been set at the end of each chap- ter. In addition, it includes seven appendices on how to procure and maintain the various organisms as well as a useful list of audio-visual aids suitable for teaching develop- mental biology.

Some teachers may find the mix- ture of experiments with living material and 'dry' literature analysis classes a little curious, while others may welcome this. My overall view is that this will prove to be a thoroughly useful production, making practical classes for developmental biology teachers much more successful and much more painless than most are accus- tomed to, especially since the experiments in the manual have been tested and corrected by several sets of students.

J.B. G ~ N

Department of Zoolopo, , University of Cambridge, Downing Street, Cambridge CB2

3EJ, UK.

TIG FEBRUARY 1989 VOt. 5 NO. 2

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