Helix stability in prokaryotic promoter regions.
Prokaryotic promoters have been extensively studied to relate sequence features to promoter function. Here we examine the relationship between double-helix stability and promoter activity. The double-helix stability is evaluated from sequence data by free energy computation, based on reported values of dinucleotide free energies for strand separation. For a collection of 168 promoters, we find that within a 500-nucleotide span around the transcription initiation site the -10 region is the least stable. There is no correlation between the free energies and the rates of RNA polymerase-promoter open complex formation measured for 25 promoters. We also compare the free energies of 121 promoter mutations across the -35 and -10 consensus regions with the free energies of the corresponding wild-type sequences. These pairwise mutant-wild-type comparisons provide a particularly good test since the examined sequences differ only in one nucleotide so that all other sequence-dependent effects remain the same. About 80% of the mutations in the -10 region that show increased/reduced promoter activity are less/more stable than the wild types. The observed high free energy peak and the mutation data strongly support the conjecture that the instability, or melting properties, of the -10 region plays a significant role in promoter function.
Margalit
H
H
Laboratory of Mathematical Biology, National Cancer Institute, Bethesda, Maryland 20892.
Shapiro
B A
BA
Nussinov
R
R
Owens
J
J
Jernigan
R L
RL
D002477:Cells / Q000032:analysis*; D007256:Information Systems; D009154:Mutation; D009690:Nucleic Acid Conformation; D011387:Prokaryotic Cells / Q000032:analysis*; D011401:Promoter Regions, Genetic; D013696:Temperature; D014158:Transcription, Genetic