The DNA-binding network of Mycobacterium tuberculosis

• Published in: Nature communications 2015-01, Vol.6 (1), p.5829-5829
• Main Authors: Minch, Kyle J., Rustad, Tige R., Peterson, Eliza J. R., Winkler, Jessica, Reiss, David J., Ma, Shuyi, Hickey, Mark, Brabant, William, Morrison, Bob, Turkarslan, Serdar, Mawhinney, Chris, Galagan, James E., Price, Nathan D., Baliga, Nitin S., Sherman, David R.
• Format: Article
• Language: English
• Subjects: 38/15; 38/23; 38/39; 38/61; 631/208/325/2482; 631/337; 692/699/255/1856; 82/83; Amino Acid Motifs; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Binding Sites; Cell division; Chromatin Immunoprecipitation; Computational Biology; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genetic Vectors; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Metabolism; multidisciplinary; Mycobacterium tuberculosis - chemistry; Mycobacterium tuberculosis - genetics; Nucleotide Motifs; Pathogens; Promoter Regions, Genetic; Protein Binding; Proteins; Recombinant Proteins - chemistry; ROC Curve; Science; Transcription factors; Transcription Factors - chemistry; Transcription, Genetic; Tuberculosis
• ISSN: 2041-1723
• DOI: 10.1038/ncomms6829

Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20–30 s. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154 TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter-binding events directly associated with proximal gene regulation. An additional ~4,200 binding events are in promoter windows and represent strong candidates for direct transcriptional regulation under appropriate environmental conditions. However, we also identify >10,000 ‘dormant’ DNA-binding events that cannot be linked directly with proximal transcriptional control, suggesting that widespread DNA binding may be a common feature that should be considered when developing global models of coordinated gene expression. Adaptation of Mycobacterium tuberculosis to the host environment is principally mediated through its transcription factors. Here, the authors report the DNA binding and transcriptional profile of ~80% of all predicted M. tuberculosis transcription factors, and find wide-spread dormant DNA binding.