Mapping and manipulating the Mycobacterium tuberculosis transcriptome using a transcription factor overexpression-derived regulatory network.

Publication Type:

Journal Article

Source:

Genome Biol, Volume 15, Issue 11, p.502 (2014)

Keywords:

Cloning, Molecular, Gene Expression Regulation, Bacterial, Gene Regulatory Networks, Humans, Isoniazid, Mycobacterium tuberculosis, Promoter Regions, Genetic, Regulon, Transcription Factors, Transcription, Genetic, Transcriptome, Tuberculosis

Abstract:

<p><b>BACKGROUND: </b>Mycobacterium tuberculosis senses and responds to the shifting and hostile landscape of the host. To characterize the underlying intertwined gene regulatory network governed by approximately 200 transcription factors of M. tuberculosis, we have assayed the global transcriptional consequences of overexpressing each transcription factor from an inducible promoter.</p><p><b>RESULTS: </b>We cloned and overexpressed 206 transcription factors in M. tuberculosis to identify the regulatory signature of each. We identified 9,335 regulatory consequences of overexpressing each of 183 transcription factors, providing evidence of regulation for 70% of the M. tuberculosis genome. These transcriptional signatures agree well with previously described M. tuberculosis regulons. The number of genes differentially regulated by transcription factor overexpression varied from hundreds of genes to none, with the majority of expression changes repressing basal transcription. Exploring the global transcriptional maps of transcription factor overexpressing (TFOE) strains, we predicted and validated the phenotype of a regulator that reduces susceptibility to a first line anti-tubercular drug, isoniazid. We also combined the TFOE data with an existing model of M. tuberculosis metabolism to predict the growth rates of individual TFOE strains with high fidelity.</p><p><b>CONCLUSION: </b>This work has led to a systems-level framework describing the transcriptome of a devastating bacterial pathogen, characterized the transcriptional influence of nearly all individual transcription factors in M. tuberculosis, and demonstrated the utility of this resource. These results will stimulate additional systems-level and hypothesis-driven efforts to understand M. tuberculosis adaptations that promote disease.</p>

Supplementary Files: 

TFOE Expression Data Records

Title Gene BioProject GEO Series Platform Accession Sample Method Sample Type References Release Date Repository
TFOE_8709_3557c
Transcriptional factor in putative operon for degradation of branched-chain alkanes, nitroalkanes and may be also cyclic ketones, alkenoic acids
PRJNA254351 GSE59086 GPL14824 GSM1427006 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_9860_3557c
Transcriptional factor in putative operon for degradation of branched-chain alkanes, nitroalkanes and may be also cyclic ketones, alkenoic acids
PRJNA254351 GSE59086 GPL14824 GSM1427007 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_3005_3574_A
Transcriptional regulator kstR (Rv3574), TetR family
PRJNA254351 GSE59086 GPL14824 GSM1427008 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_3677_3574
Transcriptional regulator kstR (Rv3574), TetR family
PRJNA254351 GSE59086 GPL14824 GSM1427009 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_4186_3574_B
Transcriptional regulator kstR (Rv3574), TetR family
PRJNA254351 GSE59086 GPL14824 GSM1427010 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_7355_3574
Transcriptional regulator kstR (Rv3574), TetR family
PRJNA254351 GSE59086 GPL14824 GSM1427011 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_8131_3574_C_3000ng
Transcriptional regulator kstR (Rv3574), TetR family
PRJNA254351 GSE59086 GPL14824 GSM1427012 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_2077_3583c
CarD-like transcriptional regulator
PRJNA254351 GSE59086 GPL14824 GSM1427013 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_3529_3583c
CarD-like transcriptional regulator
PRJNA254351 GSE59086 GPL14824 GSM1427014 Tiling Array RNA 25232098 4-Jul-14 GEO
TFOE_4902_3488
Transcriptional regulator, PadR family
PRJNA254351 GSE59086 GPL14824 GSM1427003 Tiling Array RNA 25232098 4-Jul-14 GEO