Chromatin and Transcription: Merging Package and Process

Chromatin Structure and Gene Expression, Second Edition Edited by Sarah C.R. Elgin and Jerry L. Workman Oxford: Oxford University Press (2001). 328 pp. $60.00Few active scientists can legitimately claim to remember the days when conventional wisdom held that deoxyribonucleic acid was far too simple a chemical to embody genetic information. We now smile knowingly at the quaint arguments that the four “letters” in the DNA alphabet could hardly suffice to encode the vast range of genetic characteristics inherent in any individual organism, in the differences between organisms of a species, and among the myriad species of our biotic world. The successful modeling of the structure of DNA led to the solution of the coding problem and eventually to the unraveling of the mechanisms of replication, transcription, and translation that accomplish the copying and reading of the genetic code.Not so rare are scientists who can recall a similar opprobrium being laid to chromatin. Even in early days, it was recognized that something had to package some 2 meters of linear DNA to fit within the 10 μm diameter of a human cell nucleus. The obviously redundant structure of the nucleosome (and the higher orders of chromatin structure, up to the compacted mitotic chromosomes) might certainly help to accomplish this packaging. But the genetic regulatory role of this packaging has at times been viewed as no more than an obvious steric hindrance to those elegant processes noted above.In another sense, we've known better for a long time, and so over the years most conferences on eukaryotic replication or transcriptional mechanisms included at least a few token talks on chromatin (sometimes relegated to the morning session after the closing banquet). No longer. In current discussions of the control of eukaryotic gene expression, chromatin is considered not so much a static barrier to transcription as an active participant in the delicate dance in time and space that results in the appropriate turning on and off of the right genes in the right cells at the right times in response to the right signals.Within the last five years, our knowledge and understanding of chromatin structure and its function in gene regulation has dramatically expanded. This emerging understanding has resulted from a marriage of genetic, biochemical, and molecular approaches. For example, we now have a very clear picture of the structure of the nucleosome, although the higher-order structures of chromatin remain clouded in mystery. Also, we now recognize several classes of proteins (or protein complexes) that actively modify chromatin structure. These include histone acetyltransferases (HATs) and deacetylases (HDACs), as well as ATP-dependent remodeling activities (involving SWI/SNFs and ISWIs). Interestingly, many of these proteins had been previously described with respect to their effects on transcription, thereby strengthening the link between chromatin and gene regulation. Not only have these modifying activities and the factors responsible for them been characterized, but it has also become clear that these proteins function in complexes. Many of these complexes contain a large number of (sometimes overlapping) members, suggesting a web of functional interactions that might be viewed as either elegantly integrated or hopelessly tangled.This expansion of knowledge and understanding is highlighted in the second edition of Chromatin Structure and Gene Expression, edited by Sarah C.R. Elgin and Jerry L. Workman. This text examines the effects of chromatin on transcription through a wide range of structural levels from the nucleosome to nuclear organization. Because of this breadth, laboratories focused on one particular aspect of chromatin and gene regulation may find that this book will serve as a useful reference text for information on other subfields. The book is targeted to a fairly broad audience, including beginning graduate students and scientists established in distinct research areas. However, the novice should be forewarned; whereas the first edition (published in 1995) offered a very readable summary of the major concepts in this field at that time, this new volume packs a wealth of information much more densely.The book begins with a chapter on chromatin structure, highlighting information gleaned from the crystal structure of the nucleosome and noting the continuing dearth of detail for higher-order structures. The next few chapters discuss the effects on chromatin and its assembly during replication of DNA and begin to discuss its role in transcription, setting the stage for future chapters. Apparent throughout these first chapters is a continuing discussion of nucleosomal and chromatin dynamics. The reader is introduced to chromatin proteins themselves and their variations and modifications, as well as the proteins and complexes that are responsible for nucleosome assembly and chromatin modification.Four full chapters explore chromatin-modifying activities (including the chromatin remodeling ATPase families and the acetylation and deacetylation enzymes) and their effects on gene regulation, reflecting the current research focus in these areas and the vast increase in our knowledge of these processes since the publication of the first edition. The book then addresses chromatin regulation of gene function at several higher organization levels. Three chapters discuss different forms of epigenetic regulation in yeast, Drosophila, and mammals. A chapter added to this new edition illustrates chromatin effects on the developmental regulation of genes using two examples, control of gene expression by the thyroid hormone receptor and the regulation of the β-globin locus. A chapter on chromatin boundaries discusses the role of these elements in preventing misregulation of neighboring genes as well as possible roles in organization of genomes. This concept leads very nicely into the final chapter, another new addition that deals with large-scale chromatin structure and nuclear organization and highlights many new areas of research.While the text is quite comprehensive in accommodating a wide range of biological systems, genetic pathways, and experimental approaches, one notable omission is the role of chromatin in regulation of gene expression in plants. Work in Arabidopsis is mentioned briefly in chapters on modifying complexes, an area of current investigation that will likely reveal both important similarities and differences when compared with extensive studies in yeast and other higher eukaryotes. Plants are also notable for having a higher degree of methylation throughout their genomes, and this and other epigenetic effects on gene expression (i.e., posttranscriptional gene silencing, paramutation, etc.) warrant some attention in a text such as this. The scant attention given in this text to the roles of histone variants reflects their unappreciated status in the field generally, a deficit that some might hope will be remedied in the near future.Accompanying illustrations found in each of the chapters are of excellent quality, and many appear to be original to this publication. The figures typically provide a summary of information or a model, which can be helpful either as a quick reference or as a point of clarification for the beginner. This latter notion is particularly true for tables included in the chapters on chromatin modifying activities, which help one to keep track of the various complexes.Each chapter was written by investigators from at least two different laboratories, a strategy that helps balance the depth and breadth of material. The editors are commended for the remarkable consistency throughout the book in the detail to which each topic is covered. In addition to a dialog between chapter authors, the book is further enhanced by discussions with authors of other sections, which are often reflected in the “Final Comments” at the end of each chapter. One of many positive aspects of the book is the highlighting of unanswered questions and future directions, perhaps especially critical in such a fast-changing field.Overall, this text provides a detailed introduction to various research areas concerning the interaction between chromatin function and gene regulation. At this point, these fields have not completely merged. For example, we don't fully understand how the effects of various chromatin-modifying activities on the transcriptional machinery may result in epigenetic phenomena that affect a single locus or an entire chromosome. However, the question is no longer whether chromatin structure plays an active and dynamic role in regulating gene expression, but how the complexities and intricacies of this role are accomplished. By the time we see a third edition of this useful volume, it is likely that at least some of these mechanisms will be more clearly defined.