[
Harvey Lect,
1999]
A fundamental problem in biology is to determine how small quantitative differences in molecular signals are translated into alternative developmental fates and how developmental decisions are controlled by genetic regulatory hierarchies. A separate problem is to understand how gene expression is regulated at the level of whole chromosomes. Establishing the mechanistic link between higher-order chromatin structure and the regulation of gene expression is central to understanding this problem. These biological topics are addressed in this review through experiments that reveal the mechanisms by which the model organism Caenorhabditis elegans specifies its choice of sexual fate and regulates X chromosome-wide gene expression through the process of dosage compensation.