Co-regulation Of Target Genes Research Articles

Retraction of "Quorum Sensing System in Bacteroides thetaiotaomicron Strain Identified by Genome Sequence Analysis".

[This retracts the article DOI: 10.1021/acsomega.0c03986.].

Quorum Sensing System in Bacteroides thetaiotaomicron Strain Identified by Genome Sequence Analysis.

This study is a bioinformatics assay on the microbial genome of Bacteroides thetaiotaomicron. The study focuses on the problem of quorum sensing as a result of adverse factors such as chemotherapy and antibiotic therapy. In patients with severe intestinal diseases, two strains of microorganisms were identified that were distinguished as new. Strains were investigated by conducting genome sequencing. The current concepts concerned with the quorum sensing system regulation by stationary-phase sigma factor and their coregulation of target genes in B. thetaiotaomicron were considered. The study suggested using bioinformatics data for the diagnosis of gastrointestinal disorders. In the course of the study, 402 genes having a greater than twofold change were identified with the 95% confidence level. The shortest and longest coding genes were predicted; the noncoding genes were detected. Biological pathways (KEGG pathways) were classified into the following categories: cellular processes, environmental information processing, genetic information processing, human disease, metabolism, and organismic systems. Among notable changes in the biofilm population observed in parallel to the planktonic B. thetaiotaomicron was the expression of genes in the polysaccharide utilization loci that were involved in the synthesis of O-glycans.

Improved recovery of cell-cycle gene expression in Saccharomyces cerevisiae from regulatory interactions in multiple omics data

BackgroundGene expression is regulated by DNA-binding transcription factors (TFs). Together with their target genes, these factors and their interactions collectively form a gene regulatory network (GRN), which is responsible for producing patterns of transcription, including cyclical processes such as genome replication and cell division. However, identifying how this network regulates the timing of these patterns, including important interactions and regulatory motifs, remains a challenging task.ResultsWe employed four in vivo and in vitro regulatory data sets to investigate the regulatory basis of expression timing and phase-specific patterns cell-cycle expression in Saccharomyces cerevisiae. Specifically, we considered interactions based on direct binding between TF and target gene, indirect effects of TF deletion on gene expression, and computational inference. We found that the source of regulatory information significantly impacts the accuracy and completeness of recovering known cell-cycle expressed genes. The best approach involved combining TF-target and TF-TF interactions features from multiple datasets in a single model. In addition, TFs important to multiple phases of cell-cycle expression also have the greatest impact on individual phases. Important TFs regulating a cell-cycle phase also tend to form modules in the GRN, including two sub-modules composed entirely of unannotated cell-cycle regulators (STE12-TEC1 and RAP1-HAP1-MSN4).ConclusionOur findings illustrate the importance of integrating both multiple omics data and regulatory motifs in order to understand the significance regulatory interactions involved in timing gene expression. This integrated approached allowed us to recover both known cell-cycles interactions and the overall pattern of phase-specific expression across the cell-cycle better than any single data set. Likewise, by looking at regulatory motifs in the form of TF-TF interactions, we identified sets of TFs whose co-regulation of target genes was important for cell-cycle expression, even when regulation by individual TFs was not. Overall, this demonstrates the power of integrating multiple data sets and models of interaction in order to understand the regulatory basis of established biological processes and their associated gene regulatory networks.

Abstract 5112: Foxa1 and Foxa2 are essential for gender dimorphism in liver cancer

Abstract Hepatocellular carcinoma (HCC) is sexually dimorphic in both rodents and humans, with significantly higher incidence in males, an effect that is dependent on sex hormones. The molecular mechanisms by which estrogens prevent and androgens promote liver cancer remain unclear. Here, we discover that sexually-dimorphic HCC is completely reversed in Foxa1- and Foxa2-deficient mice after diethylnitrosamine-induced hepatocarcinogenesis. Co-regulation of target genes by Foxa1/a2 and either the estrogen receptor (ERalpha) or the androgen receptor (AR) was increased during hepatocarcinogenesis in normal female or male mice, respectively, but was lost in Foxa1/2-deficient mice. Thus, both estrogen-dependent resistance to and androgen-mediated facilitation of HCC depend on Foxa1/2. Strikingly, single nucleotide polymorphisms at FOXA2 binding sites reduce binding of both FOXA2 and ERalpha to their targets in human liver, and correlate with HCC development in women. Thus, Foxa factors and their targets are central for the sexual dimorphism of HCC. (Cell, accepted in press) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5112. doi:1538-7445.AM2012-5112

Foxa1 and Foxa2 Are Essential for Sexual Dimorphism in Liver Cancer

Hepatocellular carcinoma (HCC) is sexually dimorphic in both rodents and humans, with significantly higher incidence in males, an effect that is dependent on sex hormones. The molecular mechanisms by which estrogens prevent and androgens promote liver cancer remain unclear. Here, we discover that sexually dimorphic HCC is completely reversed in Foxa1- and Foxa2-deficient mice after diethylnitrosamine-induced hepatocarcinogenesis. Coregulation of target genes by Foxa1/a2 and either the estrogen receptor (ERα) or the androgen receptor (AR) was increased during hepatocarcinogenesis in normal female or male mice, respectively, but was lost in Foxa1/2-deficient mice. Thus, both estrogen-dependent resistance to and androgen-mediated facilitation of HCC depend on Foxa1/2. Strikingly, single nucleotide polymorphisms at FOXA2 binding sites reduce binding of both FOXA2 and ERα to their targets in human liver and correlate with HCC development in women. Thus, Foxa factors and their targets are central for the sexual dimorphism of HCC.

Notch and Transforming Growth Factor-β (TGFβ) Signaling Pathways Cooperatively Regulate Vascular Smooth Muscle Cell Differentiation

Notch and transforming growth factor-beta (TGFbeta) play pivotal roles during vascular development and the pathogenesis of vascular disease. The interaction of these two pathways is not fully understood. The present study utilized primary human smooth muscle cells (SMC) to examine molecular cross-talk between TGFbeta1 and Notch signaling on contractile gene expression. Activation of Notch signaling using Notch intracellular domain or Jagged1 ligand induced smooth muscle alpha-actin (SM actin), smooth muscle myosin heavy chain, and calponin1, and the expression of Notch downstream effectors hairy-related transcription factors. Similarly, TGFbeta1 treatment of human aortic smooth muscle cells induced SM actin, calponin1, and smooth muscle protein 22-alpha (SM22alpha) in a dose- and time-dependent manner. Hairy-related transcription factor proteins, which antagonize Notch activity, also suppressed the TGFbeta1-induced increase in SMC markers, suggesting a general mechanism of inhibition. We found that Notch and TGFbeta1 cooperatively activate SMC marker transcripts and protein through parallel signaling axes. Although the intracellular domain of Notch4 interacted with phosphoSmad2/3 in SMC, this interaction was not observed with Notch1 or Notch2. However, we found that CBF1 co-immunoprecipitated with phosphoSmad2/3, suggesting a mechanism to link canonical Notch signaling to phosphoSmad activity. Indeed, the combination of Notch activation and TGFbeta1 treatment led to synergistic activation of a TGFbeta-responsive promoter. This increase corresponded to increased levels of phosphoSmad2/3 interaction at Smad consensus binding sites within the SM actin, calponin1, and SM22alpha promoters. Thus, Notch and TGFbeta coordinately induce a molecular and functional contractile phenotype by co-regulation of Smad activity at SMC promoters.

The tracheae defective gene encodes a bZIP protein that controls tracheal cell movement during Drosophila embryogenesis.

The tracheae defective (tdf) gene is required for the formation of the tracheal system during Drosophila embryogenesis. It encodes a putative bZIP transcription factor (TDF). Antibodies directed against TDF detect a nuclear protein in all tracheal cells before invagination and throughout tracheal system morphogenesis. Examination of tdf mutants revealed that tdf activity is not necessary for determining tracheal cell identity but for subsequent morphogenetic cell movements. tdf activity is under the control of trachealess, the key regulator gene for tracheal development. In contrast, tdf activity is not dependent on and does not interfere with the fibroblast growth factor- (FGF) and Decapentaplegic- (DPP) mediated signalling that direct guided tracheal cell migration. Our results suggest that lack of tdf activity affects tracheal cell migration in general rather than specific aspects of cell migration. tdf activity involves a maternal and zygotic component and its requirement is not limited to tracheal system formation. The complex spatiotemporal patterns of TDF expression in the embryo correspond to defects, suggesting that cell migration is impaired. We propose that the bZIP protein TDF functions as a co-regulator of target genes that provide cells with the ability to migrate.