title: Microsatellite instability regulates transcription factor binding and gene expression.
abstract: 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.affiliation: 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
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.forename: Katherine
authors.initials: K
authors.lastname: Makepeace
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Hill
authors.forename: Derek W
authors.initials: DW
authors.lastname: Hood
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: 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
chemical_list: D001425:Bacterial Outer Membrane Proteins; D014157:Transcription Factors
references.citation: Mol Microbiol. 2004 May;52(4):1081-90
references.pmid: 15130126
references.citation: J Infect Dis. 2004 Jun 15;189(12):2227-34
references.pmid: 15181570
references.citation: Infect Immun. 2004 Jul;72(7):4052-60
references.pmid: 15213150
references.citation: Infect Immun. 2004 Jul;72(7):4217-23
references.pmid: 15213166
references.citation: Mol Microbiol. 2004 Nov;54(3):808-22
references.pmid: 15491369
references.citation: Proc Natl Acad Sci U S A. 1984 Aug;81(16):5017-20
references.pmid: 6089170
references.citation: Curr Biol. 1994 Jan 1;4(1):24-33
references.pmid: 7922307
references.citation: Mol Microbiol. 1994 Jul;13(2):207-17
references.pmid: 7984102
references.citation: Mol Microbiol. 1995 Apr;16(1):1-7
references.pmid: 7651128
references.citation: EMBO J. 1996 Jan 2;15(1):192-8
references.pmid: 8598202
references.citation: Mol Microbiol. 1996 Apr;20(1):213-22
references.pmid: 8861218
references.citation: Trends Genet. 1997 Feb;13(2):74-8
references.pmid: 9055609
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3140-5
references.pmid: 9501229
references.citation: J Bacteriol. 1998 Apr;180(8):2152-9
references.pmid: 9555899
references.citation: Gene. 1999 Jun 11;233(1-2):49-57
references.pmid: 10375620
references.citation: Mol Microbiol. 2000 May;36(3):585-93
references.pmid: 10844648
references.citation: J Bacteriol. 2000 Jul;182(13):3802-8
references.pmid: 10850997
references.citation: Mol Microbiol. 2001 Mar;39(5):1345-55
references.pmid: 11251849
references.citation: J Bacteriol. 2002 Mar;184(5):1335-9
references.pmid: 11844762
references.citation: Mol Microbiol. 2002 Mar;43(6):1555-64
references.pmid: 11952904
references.citation: Trends Microbiol. 2002 May;10(5):227-32
references.pmid: 11973156
references.citation: Mol Cell Probes. 2002 Apr;16(2):153-8
references.pmid: 12030765
references.citation: J Exp Med. 2002 Jun 3;195(11):1445-54
references.pmid: 12045242
references.citation: J Bacteriol. 2002 Jul;184(14):3965-74
references.pmid: 12081969
references.citation: Mol Ecol. 2002 Dec;11(12):2453-65
references.pmid: 12453231
references.citation: J Bacteriol. 2003 Apr;185(8):2618-27
references.pmid: 12670987
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9542-7
references.pmid: 12883001
references.citation: Mol Microbiol. 2003 Oct;50(1):245-57
references.pmid: 14507378