edited by Martin L. Privalsky. Springer-Verlag (2001) 190 pages. ISBN 3-540-67611-2 £79/$119
Not so long ago it was thought that eukaryotic transcription was regulated entirely by activation of genes that were otherwise inert. This view has since been squelched by the burgeoning field of transcriptional repression. Transcriptional corepressors, binding to transcription factors and actively preventing transcription, are clearly important for tight control of gene expression. Martin Privalsky has brought together an outstanding group of investigators to produce a succinct yet thorough survey of this field. This collection of reviews is well organized, and describes recently discovered corepressor complexes and the mechanisms they might use to exert their repressive effects. The first chapter orients the reader to the organization of chromatin structure and how it may be altered by chromatin-remodeling activities, including the covalent modification of histones. The lucid discussion of these issues is now poignant, as well as informative, given the recent untimely death of one of the authors, Dr Alan Wolffe, a leader in this field. The second chapter, by Kuzmichev and Reinberg, focuses on multiprotein complexes containing histone deacetylases (HDACs) as critical regulators of the repressed state. Chromatin structure and HDAC complexes are appropriately featured throughout the book. Thus, the first two chapters nicely set the stage for subsequent chapters focused on corepressors in model organisms, corepressors used by specific transcription factors, and the role of corepressors in leukemia.
The chapter by Roth links classical repressors to Sin3, Tup1p and Hir corepressors in yeast. Mannervik’s chapter highlights the roles of Groucho, CtBP and HDACs in Drosophila development. Two chapters are dedicated to nuclear hormone receptors and their corepressors N-CoR and SMRT. A review by Ordentlich, Downes, and Evans describes the ability of nuclear receptors to recruit HDACs through interaction with corepressor proteins. This precedes Privalsky’s in-depth analysis of the regulation of nuclear receptor corepressor function. These chapters successfully provide continuity without redundancy. Harbour and Dean provide a very concise review of the repression characteristics of the retinoblastoma protein cell cycle transcription factor, and Wotton and Massague extensively review the role of Smad corepressors in TGFβ family signaling. In the final chapter, Guidez and Zalent explore the role of corepression in the pathogenesis of human leukemias, explaining in molecular terms how fusions of such factors as PML and PLZF with retinoic acid receptor α lead to aberrant recruitment of corepressors and dysregulation of normal cell growth and differentiation.
While the focus of this book is clearly on corepressor-complex-mediated recruitment of chromatin-modifying activities to transcription factors of choice, this is balanced in many chapters by substantial attention to alternate means of repression, such as interruption of basal factor recruitment. Overall, this book is a brief, well-written and understandable introduction to the world of transcriptional corepressors. It is a valuable reference for those in the field and is worth reading cover-to-cover by those interested in an overview of this emerging area.
