A postgenome challenge is to understand how the code in DNA is converted into the biological processes underlying various cell fates. By establishing the appropriate technical tools, we are moving from an era in which such questions have been asked by studying individual genes to one in which large domains, whole chromosomes, and the entire human genome can be investigated. These developments will allow us to study in parallel the transcriptional program and components of the epigenetic program (nuclear position, timing of replication, chromatin structure and modification, DNA methylation) to determine the hierarchy and order of events required to switch genes on and off during differentiation and development.