Efficient chromosomal-scale DNA looping in Escherichia coli using multiple DNA-looping elements.
Genes are frequently regulated by interactions between proteins that bind to the DNA near the gene and proteins that bind to DNA sites located far away, with the intervening DNA looped out. But it is not understood how efficient looping can occur when the sites are very far apart. We develop a simple theoretical framework that relates looping efficiency to the energetic cost and benefit of looping, allowing prediction of the efficiency of single or multiple nested loops at different distances. Measurements of absolute loop efficiencies for Lac repressor and λ CI using gene expression reporters in Escherichia coli cells show that, as predicted by the model, long-range DNA looping between a pair of sites can be strongly enhanced by the use of nested DNA loops or by the use of additional protein-binding sequences. A combination of these approaches was able to generate efficient DNA looping at a 200 kb distance.
Department of Molecular and Cellular Biology, University of Adelaide, North Terrace, Adelaide SA 5005, Australia.
Nan
N
Hao
Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, Copenhagen Ø 2100, Denmark.
Kim
K
Sneppen
Department of Molecular and Cellular Biology, University of Adelaide, North Terrace, Adelaide SA 5005, Australia.
Keith E
KE
Shearwin
Department of Molecular and Cellular Biology, University of Adelaide, North Terrace, Adelaide SA 5005, Australia.
Ian B
IB
Dodd
D002876:Chromosomes, Bacterial; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D056968:Lac Repressors / Q000378:metabolism; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins; D014764:Viral Proteins; C076896:repressor protein C1, bacteriophage