Dataset Information

Genome-wide localization of the polyphenol quercetin in human monocytes.

ABSTRACT: BACKGROUND:Quercetin is a polyphenol of great interest given its antioxidant activity and involvement in the immune response. Although quercetin has been well studied at the molecular level as a gene regulator and an activator of specific cellular pathways, not much attention has been given to its mechanism of action at the genome-wide level. The present study aims to characterize quercetin's interaction with cellular DNA and to show its subsequent effect on downstream transcription. RESULTS:Two massive parallel DNA-sequencing technologies were used: Chem-seq and RNA-seq. We demonstrate that upon binding to DNA or genome-associated proteins, quercetin acts as a cis-regulatory transcription factor for the expression of genes that are involved in the cell cycle, differentiation and development. CONCLUSIONS:Such findings could provide new and important insights into the mechanisms by which the dietary polyphenol quercetin influences cellular functions.

SUBMITTER: Atrahimovich D

PROVIDER: S-EPMC6652105 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genome-wide localization of the polyphenol quercetin in human monocytes.

Atrahimovich Dana D Samson Avraham O AO Barsheshet Yifthah Y Vaya Jacob J Khatib Soliman S Reuveni Eli E

BMC genomics 20190723 1

<h4>Background</h4>Quercetin is a polyphenol of great interest given its antioxidant activity and involvement in the immune response. Although quercetin has been well studied at the molecular level as a gene regulator and an activator of specific cellular pathways, not much attention has been given to its mechanism of action at the genome-wide level. The present study aims to characterize quercetin's interaction with cellular DNA and to show its subsequent effect on downstream transcription.<h4> ...[more]

PMID: 31337340

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Project description:BACKGROUND: Genome-wide prediction of protein subcellular localization is an important type of evidence used for inferring protein function. While a variety of computational tools have been developed for this purpose, errors in the gene models and use of protein sorting signals that are not recognized by the more commonly accepted tools can diminish the accuracy of their output. RESULTS: As part of an effort to manually curate the annotations of 19 strains of Shewanella, numerous insights were gained regarding the use of computational tools and proteomics data to predict protein localization. Identification of the suite of secretion systems present in each strain at the start of the process made it possible to tailor-fit the subsequent localization prediction strategies to each strain for improved accuracy. Comparisons of the computational predictions among orthologous proteins revealed inconsistencies in the computational outputs, which could often be resolved by adjusting the gene models or ortholog group memberships. While proteomic data was useful for verifying start site predictions and post-translational proteolytic cleavage, care was needed to distinguish cellular versus sample processing-mediated cleavage events. Searches for lipoprotein signal peptides revealed that neither TatP nor LipoP are designed for identification of lipoprotein substrates of the twin arginine translocation system and that the +2 rule for lipoprotein sorting does not apply to this Genus. Analysis of the relationships between domain occurrence and protein localization prediction enabled identification of numerous location-informative domains which could then be used to refine or increase confidence in location predictions. This collective knowledge was used to develop a general strategy for predicting protein localization that could be adapted to other organisms. CONCLUSION: Improved localization prediction accuracy is not simply a matter of developing better computational algorithms. It also entails gathering key knowledge regarding the host architecture and translocation machinery and associated substrate recognition via experimentation and integration of diverse computational analyses from many proteins and, where possible, that are derived from different species within the same genus.

Project description:BackgroundThe distribution and location of insertion elements in a genome is an excellent tool to track the evolution of bacterial strains and a useful molecular marker to distinguish between closely related bacterial isolates. The information about the genomic locations of IS elements is available in public sequence databases. However, the locations of mobile elements may vary from strain to strain and within the population of an individual strain. Tools that allow de novo localization of IS elements and are independent of existing sequence information are essential to map insertion elements and advance our knowledge of the role that such elements play in gene regulation and genome plasticity in bacteria.ResultsIn this study, we present an efficient and reliable method for linear mapping of mobile elements using whole-genome DNA microarrays. In addition, we describe an algorithm for analysis of microarray data that can be applied to find DNA sequences physically juxtaposed with a target sequence of interest. This approach was used to map the locations of the IS5 elements in the genome of Escherichia coli K12. All IS5 elements present in the E. coli genome known from GenBank sequence data were identified. Furthermore, previously unknown insertion sites were predicted with high sensitivity and specificity. Two variants of E. coli K-12 MG1655 within a population of this strain were predicted by our analysis. The only significant difference between these two isolates was the presence of an IS5 element upstream of the main flagella regulator, flhDC. Additional experiments confirmed this prediction and showed that these isolates were phenotypically distinct. The effect of IS5 on the transcriptional activity of motility and chemotaxis genes in the genome of E. coli strain MG1655 was examined. Comparative analysis of expression profiles revealed that the presence of IS5 results in a mild enhancement of transcription of the flagellar genes that translates into a slight increase in motility.ConclusionIn summary, this work presents a case study of an experimental and analytical application of DNA microarrays to map insertion elements in bacteria and gains an insight into biological processes that might otherwise be overlooked by relying solely on the available genome sequence data.

Dataset Information

Genome-wide localization of the polyphenol quercetin in human monocytes.

Publications

Genome-wide localization of the polyphenol quercetin in human monocytes.

Similar Datasets

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