Evidence map›Paper›PMID 25940627›Full record

ArticleNucleic acids research2015

Role of intragenic binding of cAMP responsive protein (CRP) in regulation of the succinate dehydrogenase genes Rv0249c-Rv0247c in TB complex mycobacteria.

Gwendowlyn S Knapp, Anna Lyubetskaya, Matthew W Peterson, Antonio L C Gomes, Zhuo Ma, James E Galagan, Kathleen A McDonough

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 40 citations in OpenAlex.

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  14. Frontiers in microbiology · 2020
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  15. Review
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Gwendowlyn S KnappWadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12201-2002, USA.
Anna LyubetskayaBioinformatics Program, Boston University, Boston, MA 02215, USA.
Matthew W PetersonDepartment of Biomedical Engineering, Boston, MA 02215, USA.
Antonio L C GomesBioinformatics Program, Boston University, Boston, MA 02215, USA.
Zhuo MaWadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12201-2002, USA.
James E GalaganBioinformatics Program, Boston University, Boston, MA 02215, USA Department of Biomedical Engineering, Boston, MA 02215, USA Department of Microbiology, Boston University, Boston, MA 02215, USA jgalag@bu.edu.
Kathleen A McDonoughWadsworth Center, New York State Department of Health, 120 New Scotland Avenue, PO Box 22002, Albany, NY 12201-2002, USA Department of Biomedical Sciences, University at Albany, SUNY, Albany, NY 12201, USA Kathleen.McDonough@health.ny.gov.
Boston University · USWadsworth Center · US

Funding

cAMP signaling pathways within Mycobacterium tuberculosisR01AI063499 · NIAID · WADSWORTH CENTER · PI MCDONOUGH, KATHLEEN A · 2005 to 2016
$2.8M
The genetics of metabolism in Mycobacterium tuberculosisF32GM095038 · NIGMS · WADSWORTH CENTER · PI KNAPP, GWENDOWLYN S. · 2011 to 2012
$109k
NIAID NIH HHS R01 AI063499NIGMS NIH HHS F32 GM095038NIGMS NIH HHS F32GM095038PHS HHS 5R01A1063499PHS HHS HHSN272200800059C
6 · The paper itself

Abstract

Bacterial pathogens adapt to changing environments within their hosts, and the signaling molecule adenosine 3', 5'-cyclic monophosphate (cAMP) facilitates this process. In this study, we characterized in vivo DNA binding and gene regulation by the cAMP-responsive protein CRP in M. bovis BCG as a model for tuberculosis (TB)-complex bacteria. Chromatin immunoprecipitation followed by deep-sequencing (ChIP-seq) showed that CRP associates with ∼900 DNA binding regions, most of which occur within genes. The most highly enriched binding region was upstream of a putative copper transporter gene (ctpB), and crp-deleted bacteria showed increased sensitivity to copper toxicity. Detailed mutational analysis of four CRP binding sites upstream of the virulence-associated Rv0249c-Rv0247c succinate dehydrogenase genes demonstrated that CRP directly regulates Rv0249c-Rv0247c expression from two promoters, one of which requires sequences intragenic to Rv0250c for maximum expression. The high percentage of intragenic CRP binding sites and our demonstration that these intragenic DNA sequences significantly contribute to biologically relevant gene expression greatly expand the genome space that must be considered for gene regulatory analyses in mycobacteria. These findings also have practical implications for an important bacterial pathogen in which identification of mutations that affect expression of drug target-related genes is widely used for rapid drug resistance screening.

Indexed as

Gene Expression Regulation, BacterialBacterial ProteinsBinding SitesCyclic AMP Receptor ProteinGene Expression Regulation, EnzymologicGenome, BacterialMycobacterium bovisPromoter Regions, GeneticRegulonSuccinate DehydrogenaseBacterial ProteinsCyclic AMP Receptor ProteinSuccinate Dehydrogenase

Identifiers

PMID25940627
PMCPMC4477654
OpenAlexW1627927614

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.