Microsatellite instability regulates transcription factor binding and gene expression.
Microsatellites are tandemly repeated simple sequence DNA motifs widely prevalent in eukaryotic and prokaryotic genomes. In pathogenic bacteria, instability of these hypermutable loci through slipped-strand mispairing mediates the high-frequency reversible switching of phenotype expression, i.e., phase variation. Phase-variable expression of NadA, an outer membrane protein and adhesin of the pathogen Neisseria meningitidis, is mediated by changes in the number of TAAA repeats located upstream of the core promoter of nadA. Here we report that loss or gain of TAAA repeats affects the binding of the transcriptional regulatory protein IHF to the nadA promoter. Thus, phase-variable transcription of nadA potentially incorporates interplay between stochastic (mutational) and prescriptive (classical) mechanisms of gene regulation.
Martin
Patricia
P
Molecular Infectious Diseases Group, University of Oxford Department of Paediatrics, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. martinp@necker.fr
Makepeace
Katherine
K
Hill
Stuart A
SA
Hood
Derek W
DW
Moxon
E Richard
ER
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D042822:Genomic Instability; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D001425:Bacterial Outer Membrane Proteins; D014157:Transcription Factors
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