Once again, this yielded a discrete labeling pattern rather than a homogeneous distribution throughout the nucleus. (1996) who used either Br-UTP or biotin-14 CTP to pulse-label nascent transcripts, and who then visualized the transcripts not only by light microscopy but also by electron microscopy using immuno-gold particles. These initial studies were further supported by Iborra et al. (1993) using the same methods, namely Br-UTP labeling of nascent RNA detected by immunofluorescence microscopy. Similar results were obtained by Wansink et al. Using confocal microscopy to visualize the transcripts, they found that transcription occurred at 300–500 discrete sites in the nucleus ( Jackson et al., 1993), rather than being homogeneously distributed throughout the nucleus. They exploited Br-UTP labeling to visualize mRNA synthesis in permeabilized HeLa cells that were encapsulated in agarose microbeads. The term transcription “factory” was first used in 1993 by Jackson and colleagues. Here we review first the data supporting this observation, and then discuss its potential consequence for polymerase function, gene regulation, and nuclear organization. Specifically, it is now recognized that transcription occurs at discrete foci located throughout the nucleus. However, in addition to this temporal coordination of gene transcription, there is strong experimental evidence that transcription is also spatially coordinated within each cell nucleus. These technologies have revealed temporally coordinated changes in the transcription levels of many genes in response to developmental or environmental changes. This regulation can now be monitored at thousands of genes simultaneously using high throughput microarrays and next-generation sequencing. There is also some evidence that transcription factories could help organize chromatin and nuclear structure, contributing to both the formation of chromatin loops and the clustering of active and co-regulated genes.Ĭellular processes like differentiation or the response to physiological stimuli all require coordinated and efficient regulation of many genes. Some data suggest that the polymerase molecules within a factory remain stationary relative to the transcribed DNA, which is thought to be reeled through the factory site. The factories are composed of ~4–30 RNA polymerase molecules, and are associated with many other molecules involved in transcriptional activation and mRNA processing. There is considerable evidence that transcription does not occur homogeneously or diffusely throughout the nucleus, but rather at a number of specialized, discrete sites termed transcription factories.
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