title: Global analysis of the regulon of the transcriptional repressor LexA, a key component of SOS response in Mycobacterium tuberculosis.
abstract: The DNA damage response is crucial for bacterial survival. The transcriptional repressor LexA is a key component of the SOS response, the main mechanism for the regulation of DNA repair genes in many bacteria. In contrast, in mycobacteria gene induction by DNA damage is carried out by two mechanisms; a relatively small number of genes are thought to be regulated by LexA, and a larger number by an alternate, independent mechanism. In this study we have used ChIP-seq analysis to identify 25 in vivo LexA-binding sites, including nine regulating genes not previously known to be part of this regulon. Some of these binding sites were found to be internal to the predicted open reading frame of the gene they are thought to regulate; experimental analysis has confirmed that these LexA-binding sites regulate the expression of the expected genes, and transcriptional start site analysis has found that their apparent relative location is due to misannotation of these genes. We have also identified novel binding sites for LexA in the promoters of genes that show no apparent DNA damage induction, show positive regulation by LexA, and those encoding small RNAs.
authors.affiliation: Division of Mycobacterial Research, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. k.smollett@ucl.ac.uk
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Smollett
authors.forename: Kimberley M
authors.initials: KM
authors.lastname: Smith
authors.forename: Christina
authors.initials: C
authors.lastname: Kahramanoglou
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Arnvig
authors.forename: Roger S
authors.initials: RS
authors.lastname: Buxton
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Davis
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D001665:Binding Sites; D002474:Cell-Free System; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004926:Escherichia coli / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000502:physiology*; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D012313:RNA; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein