title: Comprehensive insights into Mycobacterium tuberculosis DevR (DosR) regulon activation switch.
abstract: DevR regulon function is believed to be crucial for the survival of Mycobacterium tuberculosis during dormancy. In this study, we undertook a comprehensive analysis of the DevR regulon. All the regulon promoters were assigned to four classes based on the number of DevR binding sites (Dev boxes). A minimum of two boxes are essential for complete interaction and their tandem arrangement is an architectural hallmark at all promoters. Initial interaction of DevR with the conserved box is essential for its cooperative binding to adjacent sites bearing low to very poor sequence conservation and is the universal mechanism underlying DevR-mediated transcriptional induction. The functional importance of tandem arrangement was established by analyzing promoter variants harboring Dev boxes with altered spacing. Conserved sequence logos were generated from 47 binding sequences which included 24 newly discovered Dev boxes. In each half site of an 18-bp binding motif, G(5) and C(7) are essential for DevR binding. Finally, we show that DevR regulon induction occurs in a temporal manner and genes that are induced early are also usually powerfully induced. The information theory-based approach along with binding and temporal expression studies provide us with comprehensive insights into the complex pattern of DevR regulon activation.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Chauhan
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.forename: Alka
authors.initials: A
authors.lastname: Singh
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Jaya Sivaswami
authors.initials: JS
authors.lastname: Tyagi
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D015964:Gene Expression Regulation, Bacterial; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009711:Nucleotides / Q000032:analysis; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D018085:Regulon; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D009711:Nucleotides; D014157:Transcription Factors; D011494:Protein Kinases