Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structure-based analysis of the gene network controlled by the Salmonella RcsB response regulator

ABSTRACT: RcsB is a transcriptional regulator that controls expression of numerous genes in Enterobacteriaceae. RcsB accomplishes this role alone or in combination with auxiliary transcriptional factors independently or dependently of phosphorylation. To understand the mechanisms by which RcsB regulates such a large number of genes, we performed structural and in vitro and in vivo functional studies with different RcsB variants. Our structural data reveal that RcsB binds the promoters of rprA and flhDC genes in a dimeric active conformation, docking the DNA-binding domains into the major groove of the DNA that preform a weak read-out of the target sequence. Interestingly, comparative structural analysis shows that DNA binding may trigger the active conformation in unphosphorylated RcsB. Furthermore, RNAseq analysis performed in strains expressing wild-type or several RcsB variants provided new insights into the contribution of phosphorylation to gene regulation and assign a potential role of RcsB in regulating iron and molybdenum metabolism. Finally, we delimited the RcsB box for homodimeric active RcsB binding with sequence TN(G/A)GAN4TC(T/C)NA that can be found in promoter and intragenic regions to regulate activation or inhibition of gene transcription.

ORGANISM(S): Salmonella enterica subsp. enterica serovar Typhimurium str. SL1344

PROVIDER: GSE154668 | GEO | 2020/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene regulation by the RcsCB two-component system and the auxiliary protein TviA in S. Typhi

2009-12-11 | GSE15752 | GEO

Gene regulation by the RcsCB two-component system and the auxiliary protein TviA in S. Typhi

Project description:In response to osmolarity, Salmonella enterica serotype Typhi (S. Typhi) regulates genes required for Vi capsular antigen expression oppositely to those required for motility and invasion. Previous studies suggest that osmoregulation of motility, invasion and capsule expression is mediated through the RcsC/RcsD/RcsB phosphorelay system. Here we performed gene expression profiling and functional studies to determine the role of TviA, an auxiliary protein of the RcsB response regulator, in controlling virulence gene expression in S. Typhi. TviA repressed expression of genes encoding flagella and the invasion associated type III secretion system (T3SS-1) through repression of the flagellar regulators flhDC and fliZ, resulting in reduced invasion and reduced expression of FliC. Both RcsB and TviA reduced expression of flhDC, but only TviA altered flhDC expression in response to osmolarity. These data suggest that the auxiliary TviA protein integrates a new regulatory input into the RcsB regulon of S. Typhi, thereby altering expression of genes encoding flagella, the Vi antigen and T3SS-1 in response to osmolarity. Gene expression profiles of the S. Typhi wild-type strain, a rcsB mutant, a (delta)tviB-vexE (tviBCDEvexABCDE) mutant, and a (delta)viaB (tviABCDEvexABCDE) mutant (lacking tviA expression) was compared. Strains were cultured in SOB broth (low salt), a condition known to induce expression of TviA and the RcsCB system. Total RNA was extracted from two independent cultures (biological replicates) of each strain. cDNA was differentially labeled with Alexa Fluor 555 and 648, respectively and competitively hybridized on S.Typhimurium arrays (PFGRC, version 4). The submitted samples are biological replicates of a competitive hybridization of cDNA from the wild-type strain (Ty2) and the rcsB mutant (SW237) (GSM395580, GSM395581) or the viaB mutant (STY2) and the tviB-vexE mutant (SW74) (GSM395582, GSM395583), respectively.

2010-05-18 | E-GEOD-15752 | biostudies-arrayexpress

Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis

Project description:The regulatory specificity of enhancers and their interaction with gene promoters is thought to be controlled by their sequence and the binding of transcription factors. By studying Pitx1, a regulator of hindlimb development, we show that dynamic changes in chromatin conformation can restrict the activity of enhancers. Inconsistent with its hindlimb-restricted expression, Pitx1 is controlled by an enhancer (Pen) that shows activity in forelimbs and hindlimbs. By Capture Hi-C and three-dimensional modeling of the locus, we demonstrate that forelimbs and hindlimbs have fundamentally different chromatin configurations, whereby Pen and Pitx1 interact in hindlimbs and are physically separated in forelimbs. Structural variants can convert the inactive into the active conformation, thereby inducing Pitx1 misexpression in forelimbs, causing partial arm-to-leg transformation in mice and humans. Thus, tissue-specific three-dimensional chromatin conformation can contribute to enhancer activity and specificity in vivo and its disturbance can result in gene misexpression and disease.

2018-10-01 | GSE103676 | GEO

RcsB contributes to the distinct stress fitness between Escherichia coli O157:H7 curli variants of 1993 Hamburger-associated outbreak strains

Project description:Curli are adhesive fimbriae of Enterobactericaeae and are involved in surface attachment, cell aggregation and biofilm formation. We previously reported that natural curli variants of E. coli O157:H7 (EcO157) displayed distinct acid resistance; however, this difference was not linked to the curli fimbriae per se. Here, we investigated the underlying molecular basis of this phenotypic divergence between the curli variants. Among curli-producing (C+) variants isolated from the 1993 U.S. hamburger-associated outbreaks strains, we identified large deletions in the rcsB gene that encodes the response regulator of RcsCDB two-component signal transduction system of rcsB ,. Further comparison of stress fitness revealed that C+ variants were also significantly more sensitive to heat shock, but remained similar resistance to osmotic stress and oxidative damage as curli-deficient (C-) variants. Transcriptomics analysis uncovered a large number of differentially expressed genes between the curli variants, characterized by the enhanced expression of genes related to biofilm formation, virulence, catabolic activity and nutrients uptake, but marked decrease in transcription of genes related to various stress resistance in C+ variants. Supplying C+ variants with a functional rcsB restored cells resistance to heat shock and acid challenge, but blocked the curli production, confirming that inactivation of RcsB in C+ variants was the basis of fitness segregation within the EcO157population. This study provides an example of how genome instability of EcO157promotes the intra-population diversification, generating sub-populations carrying an array of distinct phenotypes that may confer the pathogen survival advantages in host and nonhost environments.

2012-08-31 | GSE39439 | GEO

Salmonella typhimurium igaA(T191P) and related

Project description:We have exploited a spontaneously isolated mutant IgaA(T191P) that is near-maximally activated for the Rcs system, to identify a vast set of genes that respond, and report new regulatory properties of this signaling system in Salmonella enterica serovar Typhimurium. Microarray data show that the Rcs system normally functions as a positive regulator of SPI-2 and other genes important for growth of Salmonella in macrophages, although when highly activated, the system completely represses the SPI-1/SPI-2 virulence, flagellar, and fimbrial biogenesis pathways. The auxilliary protein RcsA, which works with RcsB to positively regulate colanic acid and other target genes, not only stimulates but also antagonizes the positive regulation of many genes in the igaA mutant. We show that RcsB represses motility through the 'RcsB box' in the promoter region of the master operon flhDC, and that RcsA is not required for this regulation. Curiously, RcsB selectively stimulates expression of the flagellar Type 3 secretion genes fliPQR; an RcsAB box located downstream of fliR influences this regulation. We show that excess colanic acid impairs swimming and inhibits swarming motility, consistent with the inverse regulation of the two pathways by the Rcs system. The work was published in Journal of Bacteriology: Wang Q, Zhao Y, McClelland M, Harshey RM. The RcsCDB signaling system and swarming motility in Salmonella enterica serovar Typhimurium: dual regulation of flagellar and SPI-2 virulence genes. J Bacteriol. 2007 Sep 28; [Epub ahead of print] PMID: 17905992 [PubMed - as supplied by publisher] Keywords: Comparative genomic hybridization

2008-06-25 | GSE9584 | GEO

Salmonella typhimurium igaA(T191P) and related

2008-06-24 | E-GEOD-9584 | biostudies-arrayexpress

ChipSeq of mouse embryonic fibroblasts from conditional knock-in mouse carrying a phosphorylation-deficient S180A (SA) mutation in exon 5 of the endogenous mouse Trp53 gene locus

Project description:The mouse S180A (SA) mutation of the Trp53 is a p53 phosphorylation-deficient mutant protein with native conformation. Here we want to assess the impact of DNA binding site phosphorylation of the p53 target gene spectrum and transcriptional activity under untreated conditions and following p53 stabilization with the Mdm2 inhibitor nutlin-3a.

2020-06-04 | E-MTAB-9170 | biostudies-arrayexpress

RNAseq of mouse embryonic fibroblasts from conditional knock-in mice carrying a phosphorylation-deficient S180A (SA) mutation in exon 5 of the endogenous mouse Trp53 gene locus

2020-08-25 | E-MTAB-9171 | biostudies-arrayexpress

Comparison of IS5 Deletion mutant to E.coli Motile and NonMotile Isolates

Project description:These series of experiments compares the expression profile of the motility variants of E.coli MG1655 ( Motile and NonMotile isolates) to an isogenic E.coli MG1655 strain in which the IS5 upstream of flhDC has been deleted. The expression profiles of genes in the E.coli MG1655 motile isolate and E.coli MG1655 Non_Motile isolate also compared.

2010-06-09 | E-GEOD-2694 | biostudies-arrayexpress

DNA binding analysis of rare variants in homeodomains reveals homeodomain specificity-determining residues

Project description:Homeodomains (HDs) are the second largest class of DNA binding domains (DBDs) in eukaryotic sequence-specific transcription factors (TFs) and are the TF structural class with the largest number of disease mutations in the Human Gene Mutation Database (HGMD). Despite numerous structural studies and large-scale analyses of HD DNA binding specificity, HD-DNA recognition is still not fully understood. Here, we analyzed 92 human HD mutants, including disease-associated variants and variants of unknown significance (VUS), for their effects on DNA binding activity. Many of the variants altered DNA binding affinity and/or specificity. Structural analysis identified 14 novel specificity-determining positions, 5 of which do not contact DNA. The same missense substitution at analogous positions within different HDs exhibited different effects on DNA binding activity. Variant effect prediction tools perform moderately well in distinguishing variants with altered DNA binding affinity, but poorly in identifying those with altered binding specificity. Our results highlight the need for biochemical assays of TF coding variants and promote dozens of variants for further investigations into their pathogenicity and the development of clinical diagnostics and precision therapies.

2023-12-05 | GSE233827 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data