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Flashing a Light on the Spatial Organization of Transcription

Transient and highly dynamic clusters of RNA polymerase II form during the initiation phase of transcription. [Also see Report by Cisse et al.] It is surprising that the question of how transcription occurs in the eukaryotic cell nucleus is still a matter of controversy, given that it is such a basic cellular process. Conventional imaging of transcription sites, RNA polymerase II (Pol II), and active genes suggests that transcription occurs at discrete places in the nucleus, termed transcription factories. What has not been clear is whether these sites are preassembled structures that prefigure function and to which genes must then move to be transcribed, or whether they are self-organizing zones that form at active gene loci during the process of gene expression (1). One problem in resolving these issues has been the lack of information about the formation and stability of transcription factories in living cells—which could not be detected by conventional light microscopy with green fluorescent protein (GFP)–tagged Pol II (2). On page 664 of this issue, Cisse et al. (3) surmount this problem by using single-molecule light microscopy to determine the spatiotemporal organization of Pol II in the nucleus. Their observations of the formation of short-lived Pol II clusters that respond to transcriptional stimuli provide compelling evidence against the idea of preassembled stable transcription factories.