scholarly journals Regulation of bistability in the std fimbrial operon of Salmonella enterica by DNA adenine methylation and transcription factors HdfR, StdE and StdF

2019 ◽  
Vol 47 (15) ◽  
pp. 7929-7941 ◽  
Author(s):  
Lucía García-Pastor ◽  
María A Sánchez-Romero ◽  
Marcello Jakomin ◽  
Elena Puerta-Fernández ◽  
Josep Casadesús
Keyword(s):  
Transcription Factors ◽  
Salmonella Enterica ◽  
Logic Gate ◽  
Transcriptional Activators ◽  
Epigenetic Control ◽  
Adenine Methylation ◽  
Dam Methylation ◽  
Upstream Activating Sequence ◽  
Type Factor

AbstractBistable expression of the Salmonella enterica std operon is controlled by an AND logic gate involving three transcriptional activators: the LysR-type factor HdfR and the StdE and StdF regulators encoded by the std operon itself. StdE activates transcription of the hdfR gene, and StdF activates std transcription together with HdfR. Binding of HdfR upstream of the std promoter is hindered by methylation of GATC sites located within the upstream activating sequence (UAS). Epigenetic control by Dam methylation thus antagonizes formation of the StdE-StdF-HdfR loop and tilts the std switch toward the StdOFF state. In turn, HdfR binding hinders methylation of the UAS, permitting activation of the StdE-StdF-HdfR loop and concomitant formation of StdON cells. Bistability is thus the outcome of competition between DNA adenine methylation and the StdE-StdF-HdfR activator loop.

scholarly journals DNA Adenine Methylation Regulates Virulence Gene Expression in Salmonella enterica Serovar Typhimurium

2006 ◽  
Vol 188 (23) ◽  
pp. 8160-8168 ◽  
Author(s):  
Roberto Balbontín ◽  
Gary Rowley ◽  
M. Graciela Pucciarelli ◽  
Javier López-Garrido ◽  
Yvette Wormstone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salmonella Enterica ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Luria Bertani ◽  
Altered Expression ◽  
Virulence Gene Expression ◽  
Adenine Methylation ◽  
Dam Methylation ◽  
Serovar Typhimurium

ABSTRACT Transcriptomic analyses during growth in Luria-Bertani medium were performed in strain SL1344 of Salmonella enterica serovar Typhimurium and in two isogenic derivatives lacking Dam methylase. More genes were repressed than were activated by Dam methylation (139 versus 37). Key genes that were differentially regulated by Dam methylation were verified independently. The largest classes of Dam-repressed genes included genes belonging to the SOS regulon, as previously described in Escherichia coli, and genes of the SOS-inducible Salmonella prophages ST64B, Gifsy-1, and Fels-2. Dam-dependent virulence-related genes were also identified. Invasion genes in pathogenicity island SPI-1 were activated by Dam methylation, while the fimbrial operon std was repressed by Dam methylation. Certain flagellar genes were repressed by Dam methylation, and Dam− mutants of S. enterica showed reduced motility. Altered expression patterns in the absence of Dam methylation were also found for the chemotaxis genes cheR (repressed by Dam) and STM3216 (activated by Dam) and for the Braun lipoprotein gene, lppB (activated by Dam). The requirement for DNA adenine methylation in the regulation of specific virulence genes suggests that certain defects of Salmonella Dam− mutants in the mouse model may be caused by altered patterns of gene expression.

scholarly journals Regulation of finP Transcription by DNA Adenine Methylation in the Virulence Plasmid of Salmonella enterica

2005 ◽  
Vol 187 (16) ◽  
pp. 5691-5699 ◽  
Author(s):  
Eva M. Camacho ◽  
Ana Serna ◽  
Cristina Madrid ◽  
Silvia Marqués ◽  
Raúl Fernández ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Salmonella Enterica ◽  
Rna Stability ◽  
Virulence Plasmid ◽  
Methylation State ◽  
Adenine Methylation ◽  
Dam Methylation ◽  
Serovar Typhimurium ◽  
Dna Adenine Methylase ◽  
Gatc Site

ABSTRACT DNA adenine methylase (Dam−) mutants of Salmonella enterica serovar Typhimurium contain reduced levels of FinP RNA encoded on the virulence plasmid. Dam methylation appears to regulate finP transcription, rather than FinP RNA stability or turnover. The finP promoter includes canonical −10 and −35 modules and depends on the σ70 factor. Regulation of finP transcription by Dam methylation does not require DNA sequences upstream from the −35 module, indicating that Dam acts at the promoter itself or downstream. Unexpectedly, a GATC site overlapping with the −10 module is likewise dispensable for Dam-mediated regulation. These observations indicate that Dam methylation regulates finP transcription indirectly and suggest the involvement of a host factor(s) responsive to the Dam methylation state of the cell. We provide evidence that one such factor is the nucleoid protein H-NS, which acts as a repressor of finP transcription in a Dam− background. H-NS also restrains transcription of the overlapping traJ gene, albeit in a Dam-independent fashion. Hence, the decreased FinP RNA content found in Dam− hosts of S. enterica appears to result from H-NS-mediated repression of finP transcription.

scholarly journals Regulation of the Salmonella enterica std Fimbrial Operon by DNA Adenine Methylation, SeqA, and HdfR

2008 ◽  
Vol 190 (22) ◽  
pp. 7406-7413 ◽  
Author(s):  
Marcello Jakomin ◽  
Daniela Chessa ◽  
Andreas J. Bäumler ◽  
Josep Casadesús
Keyword(s):  
Salmonella Enterica ◽  
Bacterial Population ◽  
Phase Variation ◽  
Oral Infection ◽  
Wild Type ◽  
Adenine Methylation ◽  
Dam Methylation ◽  
Serovar Typhimurium ◽  
Dna Adenine Methylase ◽  
In The Wild

ABSTRACT DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium grown under laboratory conditions express the std fimbrial operon, which is tightly repressed in the wild type. Here, we show that uncontrolled production of Std fimbriae in S. enterica serovar Typhimurium dam mutants contributes to attenuation in mice, as indicated by the observation that an stdA dam strain is more competitive than a dam strain upon oral infection. Dam methylation appears to regulate std transcription, rather than std mRNA stability or turnover. A genetic screen for std regulators showed that the GATC-binding protein SeqA directly or indirectly represses std expression, while the poorly characterized yifA gene product serves as an std activator. YifA encodes a putative LysR-like protein and has been renamed HdfR, like its Escherichia coli homolog. Activation of std expression by HdfR is observed only in dam and seqA backgrounds. These data suggest that HdfR directly or indirectly activates std transcription. Since SeqA is unable to bind nonmethylated DNA, it is possible that std operon derepression in dam and seqA mutants may result from unconstrained HdfR-mediated activation of std transcription. Derepression of std in dam and seqA mutants of S. enterica occurs in only a fraction of the bacterial population, suggesting the occurrence of either bistable expression or phase variation.

Epigenetic control of KRAS-induced transformation by GLI transcription factors

Pancreatology ◽  
2013 ◽  
Vol 13 (2) ◽  
pp. e25
Author(s):  
M.G. Fernandez-Barrena ◽  
L.L. Almada ◽  
M.E. Fernandez-Zapico
Keyword(s):  
Transcription Factors ◽  
Epigenetic Control ◽  
Gli Transcription Factors

scholarly journals A Role for Mediator Core in Limiting Coactivator Recruitment in Saccharomyces cerevisiae

Genetics ◽  
2020 ◽  
Vol 215 (2) ◽  
pp. 407-420 ◽  
Author(s):  
Robert M. Yarrington ◽  
Yaxin Yu ◽  
Chao Yan ◽  
Lu Bai ◽  
David J. Stillman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Regulation ◽  
Transcription Factors ◽  
Gene Activation ◽  
Mediator Complex ◽  
Transcriptional Coactivator ◽  
The Core ◽  
Link Type ◽  
Upstream Activating Sequence ◽  
Eukaryotic Organisms

Mediator is an essential, multisubunit complex that functions as a transcriptional coactivator in yeast and other eukaryotic organisms. Mediator has four conserved modules, Head, Middle, Tail, and Kinase, and has been implicated in nearly all aspects of gene regulation. The Tail module has been shown to recruit the Mediator complex to the enhancer or upstream activating sequence (UAS) regions of genes via interactions with transcription factors, and the Kinase module facilitates the transition of Mediator from the UAS/enhancer to the preinitiation complex via protein phosphorylation. Here, we analyze expression of the Saccharomyces cerevisiae HO gene using a sin4 Mediator Tail mutation that separates the Tail module from the rest of the complex; the sin4 mutation permits independent recruitment of the Tail module to promoters without the rest of Mediator. Significant increases in recruitment of the SWI/SNF and SAGA coactivators to the HO promoter UAS were observed in a sin4 mutant, along with increased gene activation. These results are consistent with recent studies that have suggested that the Kinase module functions negatively to inhibit activation by the Tail. However, we found that Kinase module mutations did not mimic the effect of a sin4 mutation on HO expression. This suggests that at HO the core Mediator complex (Middle and Head modules) must play a role in limiting Tail binding to the promoter UAS and gene activation. We propose that the core Mediator complex helps modulate Mediator binding to the UAS regions of genes to limit coactivator recruitment and ensure proper regulation of gene transcription.

scholarly journals PhoP-Responsive Expression of the Salmonella enterica Serovar Typhimurium slyA Gene

2003 ◽  
Vol 185 (12) ◽  
pp. 3508-3514 ◽  
Author(s):  
Valia A. Norte ◽  
Melanie R. Stapleton ◽  
Jeffrey Green
Keyword(s):  
Transcription Factors ◽  
Salmonella Enterica ◽  
Promoter Region ◽  
External Signal ◽  
Dependent Manner ◽  
Factors Analysis ◽  
Upstream Promoter ◽  
Serovar Typhimurium ◽  
Transcription Regulators ◽  
Upstream Promoter Region

ABSTRACT The SlyA protein of Salmonella enterica serovar Typhimurium is a member of the MarR family of transcription regulators and is required for virulence and survival in professional macrophages. Isolated SlyA protein was able to bind a specific DNA target without posttranslational modification. This suggested that SlyA might not be activated by directly sensing an external signal but rather that the intracellular concentration of SlyA is enhanced in appropriate environments through the action of other transcription factors. Analysis of slyA transcription reveals the presence of a promoter region located upstream of the previously recognized SlyA repressed promoter. The newly identified upstream promoter region did not respond to SlyA but was activated by Mg(II) starvation in a PhoP-dependent manner. We present here evidence for a direct link between two transcription factors (PhoP and SlyA) crucial for Salmonella virulence.

scholarly journals A complex containing two transcription factors regulates peroxisome proliferation and the coordinate induction of beta-oxidation enzymes in Saccharomyces cerevisiae.

1997 ◽  
Vol 17 (1) ◽  
pp. 69-80 ◽  
Author(s):  
I V Karpichev ◽  
Y Luo ◽  
R C Marians ◽  
G M Small
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factors ◽  
Screening Strategy ◽  
Activation Process ◽  
Beta Oxidation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Coordinate Regulation ◽  
Upstream Activating Sequence ◽  
Complementation Groups ◽  
Acyl Coenzyme A

Expression of the POX1 gene, which encodes peroxisomal acyl coenzyme A oxidase in the yeast Saccharomyces cerevisiae, is tightly regulated and can be induced by fatty acids such as oleate. Previously we have shown that this regulation is brought about by interactions between trans-acting factor(s) and an upstream activating sequence (UAS1) in the POX1 promoter. We recently identified and isolated a transcription factor, Oaf1p, that binds to the UAS1 of POX1 and mediates its induction. A screening strategy has been developed and used to identify eight S. cerevisiae mutants, from three complementation groups, that are defective in the oleate induction of POX1. Characterization of one such mutant led to the identification of Oaf2p, a protein that is 39% identical to Oaf1p. Oaf1p and Oaf2p form a protein complex that is required for the activation of POX1 and FOX3 and for proliferation of peroxisomes. We propose a model in which these two transcription factors heterodimerize and mediate this activation process. The mutants that we have isolated, and further identification of the corresponding defective genes, provide us with an opportunity to characterize the mechanisms involved in the coordinate regulation of peroxisomal beta-oxidation enzymes.

scholarly journals Epigenetic Control of Salmonella enterica O-Antigen Chain Length: A Tradeoff between Virulence and Bacteriophage Resistance

PLoS Genetics ◽  
2015 ◽  
Vol 11 (11) ◽  
pp. e1005667 ◽  
Author(s):  
Ignacio Cota ◽  
María Antonia Sánchez-Romero ◽  
Sara B. Hernández ◽  
M. Graciela Pucciarelli ◽  
Francisco García-del Portillo ◽  
...  
Keyword(s):  
Chain Length ◽  
Salmonella Enterica ◽  
Epigenetic Control ◽  
Bacteriophage Resistance ◽  
O Antigen

scholarly journals Dam and its role in pathogenicity of Salmonella enterica

2009 ◽  
Vol 3 (07) ◽  
pp. 484-490 ◽  
Author(s):  
Mónica N. Giacomodonato ◽  
Sebastián H. Sarnacki ◽  
Mariángeles Noto Llana ◽  
M. Cristina Cerquetti
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Salmonella Enterica ◽  
Bacterial Pathogens ◽  
General Strategy ◽  
Essential Factor ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Dam Methylation

Dam methylation is an essential factor involved in the virulence of an increasing number of bacterial pathogens including Salmonella enterica. Lack of Dam methylation causes severe attenuation in animal models. It has been proposed that dysregulation of Dam activity is potentially a general strategy for the generation of vaccines against bacterial pathogens. In this review, we focus our attention on the role of methylation by Dam protein in regulating bacterial gene expression and virulence in Salmonella enterica.

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