The DNA-binding network of Mycobacterium tuberculosis

@article{Minch2015TheDN,
  title={The DNA-binding network of Mycobacterium tuberculosis},
  author={Kyle J. Minch and Tige R. Rustad and Eliza J. R. Peterson and Jessica K. Winkler and David J. Reiss and Shuyi Ma and Mark J. Hickey and William Brabant and Bob Morrison and Serdar Turkarslan and Chris Mawhinney and James E. Galagan and Nathan D. Price and Nitin S. Baliga and David R. Sherman},
  journal={Nature Communications},
  year={2015},
  volume={6}
}
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… 

A comprehensive map of genome-wide gene regulation in Mycobacterium tuberculosis

TLDR
This study constructed the first systems-scale map of transcription factor binding sites and their regulatory target proteins in MTB, and describes the use of TF overexpression datasets to validate a global gene regulatory network model of MTB and describes an online source to explore the datasets.

Global mapping of MtrA-binding sites links MtrA to regulation of its targets in Mycobacterium tuberculosis.

TLDR
The data have uncovered new MtrA targets that suggest that M trA is required for a transcriptional response that likely enables M. tuberculosis to persist within its host and emerge out of dormancy when the conditions are favourable.

Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the global transcriptional regulator Lsr2

TLDR
It is established that depletion of PknB in replicating M. tuberculosis results in transcriptional adaptations that implicate the DNA-binding protein Lsr2 in coordinating these changes, and that phosphorylation of LSR2 at threonine 112 is important for M.culosis growth and survival under hypoxic conditions.

AbmR is a mycobacterial dual-function transcription factor and ribonucleoprotein with distinct DNA and RNA-binding determinants

TLDR
The findings indicate that AbmR is a dual-function protein that may have novel RNA regulatory roles in stress adapted Mtb and establish a paradigm wherein a transcription factor assembles into large complexes to transition between mutually exclusive DNA-binding gene regulatory and RNA-binding RNA modulatory functions.

Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

TLDR
It is shown that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others.

Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112

TLDR
It is observed that depletion of PknB resulted in specific transcriptional changes that are likely caused by reduced phosphorylation of the H‐NS‐like regulator LSR2 at threonine 112, which controls Mtb growth and adaptations to the changing host environment by phosphorylating the global transcriptional regulator Lsr2.

Integrated Modeling of Gene Regulatory and Metabolic Networks in Mycobacterium tuberculosis

TLDR
A genome-scale regulatory-metabolic model for MTB using the Probabilistic Regulation of Metabolism (PROM) framework is expanded and improves performance of knockout growth defect predictions compared to the original PROM MTB model, and it can successfully predict growth defects associated with TF overexpression.

In silico simulations of occurrence of transcription factor binding sites in bacterial genomes

TLDR
It is speculated that transcription factor binding sites randomly occurring throughout the genome could be beneficial in promoting emergence of new regulatory interactions and thus facilitating evolution of gene regulatory networks.

New Targets and Cofactors for the Transcription Factor LrpA from Mycobacterium tuberculosis.

TLDR
This is the first report regarding that an Lrp-like protein can sense vitamins as an environmental signal, which provides a potential mechanism for tuberculosis supplementary treatment with vitamins.
...

References

SHOWING 1-10 OF 61 REFERENCES

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

TLDR
A systems-level framework describing the transcriptome of a devastating bacterial pathogen is described, the transcriptional influence of nearly all individual transcription factors in M. tuberculosis is characterized, and the phenotype of a regulator that reduces susceptibility to a first line anti-tubercular drug is validated.

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis

TLDR
Evidence is provided that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve a function similar to the Enterobacteriaceae H-NS, likely coordinating global gene regulation and virulence in this group of medically important bacteria.

A high-resolution network model for global gene regulation in Mycobacterium tuberculosis

TLDR
A rational, model-driven approach to unearth novel MTB biology that operates under some but not all phases of infection, including 23 genes that are essential to host-pathogen interactions.

Long range transcriptional control of virulence critical genes in Mycobacterium tuberculosis by nucleoid-associated proteins?

TLDR
EspR has DNA binding characteristics similar to those of nucleoid-associated proteins (NAPs) and joins two other NAP-like proteins, Lsr2 and CRPMt, in regulating expression of this operon, and is positively regulated by the EspR transcription factor.

Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis

TLDR
Results demonstrate that Rv3133c/DosR is a transcription factor of the two‐component response regulator class, and that it is the primary mediator of a hypoxic signal within M. tuberculosis.

Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRPMt as a transcription factor

TLDR
Analysis by RNA sequencing revealed widespread changes in transcriptional profile in a mutant strain lacking CRPMt during exponential growth, and in response to nutrient starvation, as well as a pattern resembling canonical CRP regulation in Escherichia coli.

Global Analysis of the Regulon of the Transcriptional Repressor LexA, a Key Component of SOS Response in Mycobacterium tuberculosis*

TLDR
This investigation identified new aspects of LexA regulation in M. tuberculosis, including nine regulating genes not previously known to be part of this regulon, and 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.

A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis

TLDR
It is concluded that this regulator, designated elsewhere as kstR, controls the expression of genes used for utilizing diverse lipids as energy sources, possibly imported through the mce4 system.
...