Microsatellite instability regulates transcription factor binding and gene expression.

Journal article

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.

Authors: Martin, P; Makepeace, K; Hill, SA; Hood, D; Moxon, E

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 102
• Issue: 10
• Pages: 3800-3804
• Publication date: 2005-03-01
• DOI: 10.1073/pnas.0406805102
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Genomic Instability; Promoter Regions, Genetic; Molecular Sequence Data; Amino Acid Sequence; Base Sequence; Transcription Factors; Gene Expression Regulation, Bacterial; Transcription, Genetic; Neisseria meningitidis; Bacterial Outer Membrane Proteins; Microsatellite Repeats