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| Status |
Public on Apr 02, 2012 |
| Title |
Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein |
| Organism |
Mycobacterium tuberculosis |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or negatively, including a key ESX-1 component, the espACD operon. EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in ChIP-Seq experiments (chromatin immunoprecipitation followed by ultra-high throughput DNA sequencing) we show that EspR binds to at least 165 loci on the Mtb genome. Included in the EspR regulon are genes encoding not only EspA, but also EspR itself, the ESX-2 and ESX-5 systems, a host of diverse cell wall functions, such as production of the complex lipid PDIM (phenolthiocerol dimycocerosate) and the PE/PPE cell-surface proteins. EspR binding sites are not restricted to promoter regions and can be clustered. This suggests that rather than functioning as a classical regulatory protein EspR acts globally as a nucleoid-associated protein capable of long-range interactions consistent with a recently established structural model. EspR expression was shown to be growth phase-dependent, peaking in the stationary phase. Overexpression in Mtb strain H37Rv revealed that EspR influences target gene expression both positively or negatively leading to growth arrest. At no stage was EspR secreted into the culture filtrate. Thus, rather than serving as a specific activator of a virulence locus, EspR is a novel nucleoid-associated protein, with both architectural and regulatory roles, that impacts cell wall functions and pathogenesis through multiple genes.
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| Overall design |
ChIP-Seq of EspR in Mtb H37Rv at mid-log phase of growth. Two independent experiments were performed. Input DNA (No IP) was used as a control.
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| Contributor(s) |
Blasco B, Chen JM, Hartkoorn R, Sala C, Uplekar S, Rougemont J, Pojer F, Cole ST |
| Citation(s) |
22479184 |
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| Submission date |
Jan 17, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Benjamin Blasco |
| E-mail(s) |
[email protected]
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| Organization name |
EPFL
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| Department |
SV-GHI
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| Lab |
UPCOL
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| Street address |
Station 19
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL15138 |
Illumina Genome Analyzer IIx (Mycobacterium tuberculosis) |
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| Samples (3) |
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| Relations |
| SRA |
SRP010364 |
| BioProject |
PRJNA150767 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35149_EspR_merged.bed.gz |
25.4 Mb |
(ftp)(http) |
BED |
| GSE35149_RAW.tar |
114.3 Mb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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