Let's talk about sex... detemination

TRENDS in Genetics Vol.17 No.10 October 2001

http://tig.trends.com

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Let’s talk about sex...

detemination

Genes and Mechanisms in Vertebrate Sex

Determination

edited by G. Scherer and M. SchmidBirkhauser, 2001. $109.00 hbk (224 pages)ISBN 3 7643 6168 9

The year 1990 sawthe end of the longsearch for themammalianY-chromosometestis-determiningfactor with thecloning of the SRYgene. The discoveryof this gene, whichencodes a DNA-binding protein,

could have been the start of a nice, easysuccess story – finding SRY target genes,understanding its biochemical function andrapidly cloning homologous genes from thesex chromosomes of other vertebrates.

More than ten years later, however, weare not much further on. No target genehas been isolated and very little is knownabout the SRY protein function.Furthermore, it appears that SRY isspecific to mammals and has nohomologue in other vertebrates. The storyhas been complicated further by thediscovery of other sex-determining genes –SOX9, SF-1, WT-1, DAX-1 and DMRT-1 –all of which encode transcription factors,however, their relationship to SRYfunction is not clearly understood. Sotoday we remain with a starting point,SRY, and a goal, the activation of the anti-Müllerian hormone (AMH ) gene in theembryonic Sertoli cells. But we knowsurprisingly little of the intermediatesteps, or indeed how many such stepsthere might be.

In Genes and Mechanisms in VertebrateSex Determination, G. Scherer and M.Schmid compile the opinions from the bestspecialists to give a comprehensiveoverview of the current knowledge in thefield. The book is logically divided inchapters corresponding to the majorvertebrate classes. The section dedicatedto mammals is the most detailed becausehuman and mouse genetics and in vitrowork have been the driving force forstudies on sex determination. However,

the sections dealing with other vertebratesare equally enlightening and interesting.

Cases of hermaphroditism or sex-reversal in humans have long fascinatedscientists. Recent developments havegenerated a wealth of informationallowing partial dissection of the sex-determination pathway. Researchers arenow trying to organize the hierarchybetween the different transcriptionfactors: ‘which one activates or repressesmy favourite gene?’ is a common question.However, the story would be a bit toosimple if it involved only transcriptionalregulation. Sex determination alsorequires contributions from otherprocesses, such as sex-specific cellularmigration, cell-to-cell interactions, sub-cellular translocation andphosphorylation of proteins.

Nevertheless, after reading the firstchapters dedicated to mammals, one startsto build a clearer model of the mechanismscontrolling sex determination. Thefollowing chapters let you discover anothertroubling aspect of the vertebrate sex-determining mechanisms: inconsistency.In contrast to other developmentalprocesses, where tissue determination anddifferentiation processes are highlyconserved among vertebrates and beyond,sex determination breaks the convenientrule of parsimony in Nature. The first pieceof the puzzle, SRY, is present only inmammals, not in birds, amphibians,reptiles or fish. Moreover, the expressionprofiles, and probably the functions, ofother factors such as SOX9, SF-1, DMRT-1and DAX-1 are not highly conserved. Forexample, SOX9, which controls theinduction of the mammalian AMH gene, isexpressed after AMH in birds! The piecesof the puzzle seem to be conserved, but theorder of the pieces varies among vertebrateclasses. Furthermore, some reptiles,crocodiles and turtles, have anenvironmental epigenetic factor,temperature, to replace genetic control ofsexual dimorphism.

In conclusion, this book is a very goodsummary of the actual knowledge (in allits complexity!) of the vertebrate sex-determining mechanisms in mammals,birds, reptiles, amphibians and fish, each reviewed in detail by the field’sexperts. Finally, I would like to express my sorrow for the loss of the late SusumuOhno, who died while the book was beingcompiled and to the memory of whom thisbook is dedicated.

Francis Poulat

Institut de Génétique Humaine, UPR CNRS,1141, 141 rue de la Cardonille,34396 Motpelier , Cedex 5, France.e-mail: Francis.Poulat@igh.cnrs.fr

PARP regulation of

eukaryotic gene

expression. Survival or

death?

From DNA Damage and Stress Signalling

to Cell Death: Poly(ADP-ribosyl)ation

Reactions

by Gilbert de Murcia and Sidney ShallOxford University Press, 2000. $125.00 hbk(238 pages) ISBN 0 19 850633 3

The covalentpoly(ADP-ribosyl)ation ofeukaryotic DNA-binding proteins isa post-translationalmodificationimplicated in themodulation ofchromatinstructure andfunction, in both

DNA-damaged and apoptotic cells1,2.Following DNA-strand breakage, thesynthesis of chromatin-bound poly(ADP-ribose) from βNAD+ is mainly catalyzed bypoly(ADP-ribose) polymerase-1 (PARP-1).For a long time, this protein was believedto be solely responsible for the synthesis ofADP-ribose chains in eukaryotic nuclei(with the exception of yeast, whichapparently lacks an ADP-ribosepolymerizing activity). However, over thepast four years, and especially since the12th International Symposium on protein-poly(ADP-ribosyl)ation3, other lessabundant PARP-like proteins have beenidentified4–7.

The poly(ADP-ribosyl)ation of PARP-1itself8, as well as the poly(ADP-ribose)modification of sequence-specific DNA-binding transcription factors9 andtelomeric proteins7, can lead to changes ingene expression patterns9,10 and theelongation of telomeres11, respectively.Therefore, the biological function ofprotein poly(ADP-ribosyl)ation appears tobe its molecular role in the maintenance ofgenomic integrity.