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Predicting three-dimensional genome structure from transcriptional activity

We would like to be able to predict how genomes are folded in the cell from the primary DNA sequence. A model for the three-dimensional structure of all genomes is presented; it is based on the structure of the bacterial nucleoid, where RNA polymerases cluster and loop the DNA. Loops appear and disappear as polymerases initiate and terminate, but the microscopic structure is 'self-organizing' and, to some extent, predictable. At the macroscopic level, transcriptional activity drives pairing between homologous sequences, inactivity allows genome compaction, and the segregation machinery orients whole chromosomes.

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Figure 1: Models of genome structure.
Figure 2: Some design principles.
Figure 3: Active polymerases are immobilized and clustered.
Figure 4: Principal factors affecting position.

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Acknowledgements

I thank the Wellcome Trust for support and A. Pombo and M. Lloyd for providing figures and software.

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Cook, P. Predicting three-dimensional genome structure from transcriptional activity. Nat Genet 32, 347–352 (2002). https://doi.org/10.1038/ng1102-347

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