Transcription factories in a Hela cell [from Cook PR (1999) Science 284, 1790]

Nuclear Structure and Function Research Group

Images / Model for all genomes

In bacteria, transcription of the circular chromosome, followed by clustering of polymerases (ovals), transcriptional activators/repressors (diamonds), and transcripts (wavy red lines), generates loops. Only one of a number of rosettes is shown, and the path of the DNA is expected to be complicated (e.g., genes a, b, c, plus p, q, and r might all be attached to rosette 1, and genes d, e, f, plus s and t to rosette 2).

In eukaryotes (and specifically in a HeLa cell), DNA is coiled around the histone octamer, and runs of nucleosomes form a zig-zagging string. At the intermediate level in the hierarchy, this string is organized into loops (average contour length 86 kbp; range 5-200 kbp) by attachment to transcriptional activators/repressors (diamonds) and engaged RNA polymerases (ovals) bound to a factory. [There will be many other ties, in addition to these major ones.] 10-20 such loops (only a few are shown) form a cloud or rosette around the factory, to give a structure equivalent to that of the bacterial nucleoid. [As in the panel on the left, active transcription units that are nearest neighbours are shown bound to one factory here, but the structure is more complex; units distant on the genetic map (perhaps on different chromosomes) will sometimes bind to one factory.]
Active polymerases do not track along their templates; they are bound to a transcription factory and act both as motors that reel in their templates and as one of the critical structural ties that maintain the loops. Loops inevitably appear and disappear as polymerases initiate and terminate, and the factors bind and dissociate. Nucleosomes in long loops are static and acquire a (heterochromatic) histone code that spreads down the fibre, they also aggregate on to the lamina, nucleoli, and chromocentres.
Each transcription factory contains one type of RNA polymerase (i.e., I, or II, or III) to the exclusion of others, and some factories are richer in certain transcription factors (i.e., activators/repressors) than others (and so are involved in the transcription of specific sets of genes). [In the nucleus, different factories are shown as spheres of different colours.] Individual components in the factory exchange continually with others in the soluble pool. 50-200 successive clouds strung along the chromosome form a territory (the general path of DNA between clouds is shown).
Go to a model for one polymerizing complex in a factory.
Go to a 5-min YouTube movie showing how we think an RNA polymerase works, how genes are regulated, and how the genome is organized.

In both cases, structure determines function (and vice versa); genes tethered close to a factory are more likely to initiate than distant ones.

Some reviews:
Cook, P.R. (2001) 'Principles of nuclear structure and function'. J. Wiley and Sons, New York. [Publisher's and local pages]
Cook, P.R. (2010). A model for all genomes; the role of transcription factories. J. Mol. Biol. 395, 1–10. [PubMed] [pdf]
Papantonis, A., and Cook, P.R. (2013). Transcription factories; genome organization and gene regulation. Chem. Rev. 113, 8683-8705. [PubMed] [pdf]

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