Prokaryotic genomes are contained in a cellular structure termed the nucleoid. However, despite a complete genome sequence and years of intensive study of Escherichia coli, our knowledge of nucleoid structure remains quite rudimentary. Moreover, little is known about the in vivo relationship between nucleoid structure and global gene regulation. Recent studies have shown that the structure of the nucleoid responds dynamically to changing environmental conditions and that this metastable nature of the nucleoid is mediated to a large extent by the distribution and activity of RNA polymerase (RNAP). For example, during rapid growth, the nucleoid is highly condensed with RNAP concentrated into transcription foci or factories, structures analogous to the eukaryotic nucleolus, where active transcription of rRNA genes occurs. However, during nutrient starvation and/or limitation, RNAP is redistributed throughout the genome and this is accompanied by a decondensation of the nucleoid. Thus, the distribution of RNAP, global gene regulation and the dynamic structure of the nucleoid are coupled in the bacterial cell. (c) 2006 Elsevier Inc. All rights reserved.