scholarly journals Phase variation of a Type IIG restriction-modification enzyme alters site-specific methylation patterns and gene expression inCampylobacter jejunistrain NCTC11168

2016 ◽  
Vol 44 (10) ◽  
pp. 4581-4594 ◽  
Author(s):  
Awais Anjum ◽  
Kelly J. Brathwaite ◽  
Jack Aidley ◽  
Phillippa L. Connerton ◽  
Nicola J. Cummings ◽  
...  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonor Sánchez-Busó ◽  
Daniel Golparian ◽  
Julian Parkhill ◽  
Magnus Unemo ◽  
Simon R. Harris

Abstract Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5′-GCAGA-3′, different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.


2019 ◽  
Author(s):  
Leonor Sánchez-Busó ◽  
Daniel Golparian ◽  
Julian Parkhill ◽  
Magnus Unemo ◽  
Simon R. Harris

ABSTRACTRestriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has experimentally inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAX as 5’-GCAGA-3’, different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.


2019 ◽  
Vol 201 (15) ◽  
Author(s):  
M. De Ste Croix ◽  
K. Y. Chen ◽  
I. Vacca ◽  
A. S. Manso ◽  
C. Johnston ◽  
...  

ABSTRACTStreptococcus pneumoniaeis one of the world’s leading bacterial pathogens, causing pneumonia, septicemia, and meningitis. In recent years, it has been shown that genetic rearrangements in a type I restriction-modification system (SpnIII) can impact colony morphology and gene expression. By generating a large panel of mutant strains, we have confirmed a previously reported result that the CreX (also known as IvrR and PsrA) recombinase found within the locus is not essential forhsdSinversions. In addition, mutants of homologous recombination pathways also undergohsdSinversions. In this work, we have shown that these genetic rearrangements, which result in different patterns of genome methylation, occur across a wide variety of serotypes and sequence types, including two strains (a 19F and a 6B strain) naturally lacking CreX. Our gene expression analysis, by transcriptome sequencing (RNAseq), confirms that the level ofcreXexpression is impacted by these genomic rearrangements. In addition, we have shown that the frequency ofhsdSrecombination is temperature dependent. Most importantly, we have demonstrated that the other known pneumococcal site-specific recombinases XerD, XerS, and SPD_0921 are not involved inspnIIIrecombination, suggesting that a currently unknown mechanism is responsible for the recombination of these phase-variable type I systems.IMPORTANCEStreptococcus pneumoniaeis a leading cause of pneumonia, septicemia, and meningitis. The discovery that genetic rearrangements in a type I restriction-modification locus can impact gene regulation and colony morphology led to a new understanding of how this pathogen switches from harmless colonizer to invasive pathogen. These rearrangements, which alter the DNA specificity of the type I restriction-modification enzyme, occur across many different pneumococcal serotypes and sequence types and in the absence of all known pneumococcal site-specific recombinases. This finding suggests that this is a truly global mechanism of pneumococcal gene regulation and the need for further investigation of mechanisms of site-specific recombination.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karolina Stępniak ◽  
Magdalena A. Machnicka ◽  
Jakub Mieczkowski ◽  
Anna Macioszek ◽  
Bartosz Wojtaś ◽  
...  

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.


1983 ◽  
Vol 258 (17) ◽  
pp. 10805-10811 ◽  
Author(s):  
M L Johnson ◽  
J Levy ◽  
S C Supowit ◽  
L Y Yu-Lee ◽  
J M Rosen

2016 ◽  
Vol 56 (3) ◽  
pp. 1107-1116 ◽  
Author(s):  
Kiyoshi Misawa ◽  
Daiki Mochizuki ◽  
Shiori Endo ◽  
Masato Mima ◽  
Yuki Misawa ◽  
...  

1990 ◽  
Vol 18 (1) ◽  
pp. 157-161 ◽  
Author(s):  
Jeffery C. Hanvey ◽  
Mitsuhiro Shimizu ◽  
Robert D. Wells

2002 ◽  
Vol 70 (2) ◽  
pp. 787-793 ◽  
Author(s):  
Patricia Guerry ◽  
Christine M. Szymanski ◽  
Martina M. Prendergast ◽  
Thomas E. Hickey ◽  
Cheryl P. Ewing ◽  
...  

ABSTRACT The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM2 and GM3 gangliosides, with minor amounts of structures mimicking GD1b and GD2. Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM2 to GM3 ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM3 ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells.


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