Chromosomes and gene expression mechanisms Theory and experiment Editorial overview Barbara Meyer and Jonathan Widom Current Opinion in Genetics & Development 2005, 15:113–115 Available online 3rd March 2005 0959-437X/$ – see front matter # 2005 Elsevier Ltd. All rights reserved. DOI 10.1016/j.gde.2005.02.008 Barbara Meyer Howard Hughes Medical Institute and Department of Molecular and Cell Biology, UC Berkeley, 16 Barker Hall, Berkeley, CA 94720-3204, USA e-mail: bjmeyer@berkeley.edu Barbara Meyer studies sex determination, X-chromosome dosage compensation, and chromosome segregation in Caenorhabditis elegans. Jonathan Widom Department of Biochemistry, Molecular Biology and Cell Biology, and Department of Chemistry, Northwestern University, 2205 Tech Drive, Evanston, IL 60208-3500, USA e-mail: j-widom@northwestern.edu Jonathan Widom studies chromosome structure and gene regulation. Introduction Gene expression is a quantitative problem. Genes are not ‘on’ or ‘off’; rather, their expression is measured by probabilities of transcript initiation and elongation per unit time and by the resulting number of mRNA molecules for a given gene in a given cell in a given window of time. In some cases, the quantitative regulation might cover expression levels over many orders of magnitude, approximating ‘on/off’ or switch-like behavior. In other cases, regulation might be quantitatively subtle in magnitude or in spatial or temporal extent, yet still be vitally important. The two-fold effects of dosage compensation and haplo-insufficiency diseases remind us of the critical consequences of modest quantitative changes in expression levels. Even smaller quantitative changes in expression have important ramifica- tions. Experimentalists are responding to the need for quantitative, systematic data by developing and applying new technologies that enable us to measure the concentrations of some or almost all of the mRNAs, specific DNA- or RNA-binding proteins, the occupancies of these proteins, and the specifi- cally modified forms of these proteins in a population of cells or, increas- ingly, in individual cells. As a result of these efforts, we have much information. However, the collection of facts does not, on its own, constitute understanding. Rather, one needs to consolidate the many facts with ideas, and link them together into a theory that accounts for the facts and makes specific, testable, quantitative predictions. At the same time, entire new gene-regulatory phenomena are being dis- covered experimentally, with breathtaking frequency. Thus, a growing need has emerged simply for more facts. And some of these facts are so surprising that we hardly know what to think about them. Thus, a pressing need also exists for new ideas and theories to understand and interpret the facts. This issue of Current Opinion in Genetics and Development highlights the progress across these many levels in the rapidly evolving field of chromo- somes and gene expression mechanisms. Quantitative analysis of regulatory circuit elements: applications to prokaryotic systems In the first of a pair of papers, Bintu et al. provide a unified theoretical analysis of all the most common forms of gene regulation in prokaryotes: regulation involving activators, repressors, cooperativity, DNA looping, or combinations of these forms. In their second paper, they apply these ideas to several of the classic prokaryotic gene regulatory systems. Their analysis is www.sciencedirect.com Current Opinion in Genetics & Development 2005, 15:113–115