Regulation Of Gene Expression Patterns Research Articles

Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila Melanogaster.

Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms.

Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits.

Birds display advanced behaviors, including vocal learning and problem-solving, yet lack a layered neocortex, a structure associated with complex behavior in mammals. To determine whether these behavioral similarities result from shared or distinct neural circuits, we used single-cell RNA sequencing to characterize the neuronal repertoire of the songbird song motor pathway. Glutamatergic vocal neurons had considerable transcriptional similarity to neocortical projection neurons; however, they displayed regulatory gene expression patterns more closely related to neurons in the ventral pallium. Moreover, while γ-aminobutyric acid-releasing neurons in this pathway appeared homologous to those in mammals and other amniotes, the most abundant avian class is largely absent in the neocortex. These data suggest that songbird vocal circuits and the mammalian neocortex have distinct developmental origins yet contain transcriptionally similar neurons.

A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control.

We have analyzed the link between the gene regulation and growth during the early stages of flower development in Arabidopsis. Starting from time-lapse images, we generated a 4D atlas of early flower development, including cell lineage, cellular growth rates, and the expression patterns of regulatory genes. This information was introduced in MorphoNet, a web-based platform. Using computational models, we found that the literature-based molecular network only explained a minority of the gene expression patterns. This was substantially improved by adding regulatory hypotheses for individual genes. Correlating growth with the combinatorial expression of multiple regulators led to a set of hypotheses for the action of individual genes in morphogenesis. This identified the central factor LEAFY as a potential regulator of heterogeneous growth, which was supported by quantifying growth patterns in a leafy mutant. By providing an integrated view, this atlas should represent a fundamental step toward mechanistic models of flower development.

Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women

Recurrent implantation failure (RIF) is the repeated failure of good-quality embryos in implantation process following several assisted reproduction cycles. Disruption of the endometrial receptivity is one of the main causes of RIF. Progesterone plays a pivotal role in the endometrial receptivity through the regulation of gene expression pattern by binding to its receptors in the endometrial cells. The aim of this study was to evaluate the expression level of progesterone receptor (PR) and its phosphorylated form in the endometrial stromal cells (eSC) of RIF patients and compare it to the eSC of healthy fertile women as control group. After isolation of the eSC from biopsy samples of RIF patients and healthy fertile women and their characterization, expression levels of PR mRNA, PR protein, and phospho-Ser294 PR protein were evaluated by quantitative real-time PCR and immunofluorescence staining, respectively. The results demonstrated a significant reduction in PR mRNA expression (P < 0.01.) and phospho-Ser294 PR protein (P < 0.05) level in RIF patients compared to the control group. These data for the first time suggest that the expression of PR and its phosphorylated form are impaired in RIF patients. Therefore, designing therapeutic methods for improving PR expression status and its regulation in the endometrium of RIF patients may help in improving the final reproductive outcomes of these cases.

ZNF143 mediates CTCF-bound promoter\u2013enhancer loops required for murine hematopoietic stem and progenitor cell function

CCCTC binding factor (CTCF) is an important factor in the maintenance of chromatin–chromatin interactions, yet the mechanism regulating its binding to chromatin is unknown. We demonstrate that zinc finger protein 143 (ZNF143) is a key regulator for CTCF-bound promoter–enhancer loops. In the murine genome, a large percentage of CTCF and ZNF143 DNA binding motifs are distributed 37 bp apart in the convergent orientation. Furthermore, deletion of ZNF143 leads to loss of CTCF binding on promoter and enhancer regions associated with gene expression changes. CTCF-bound promoter–enhancer loops are also disrupted after excision of ZNF143. ZNF143-CTCF-bound promoter–enhancer loops regulate gene expression patterns essential for maintenance of murine hematopoietic stem and progenitor cell integrity. Our data suggest a common feature of gene regulation is that ZNF143 is a critical factor for CTCF-bound promoter–enhancer loops.

Morphogenesis of a Dissected Birch Leaf in vitro Culture

The Betula pendula f. “dalecarlica” is a variety of silver birch (B. pendula) that has dissected leaves. The possible nature of the disturbance of leaf morphogenesis (the transition from a dissected shape to a normal whole leaf) in one of the eight clones of Betula “dalecarlica” during in vitro cultivation was investigated. Karyological analysis revealed a higher degree of chromatin compaction of metaphase chromosomes in the revertant clone versus the clone with dissected leaves. Reversion to the wild type is suggested to have an epigenetic nature. This is indicated by a pronounced reaction (appearance of leaves with dissection) of the explants of the revertant clone to the effect of the 5-azacytidine epimutagen (which has a demethylating effect on DNA) and a significant increase (by six times) in the proportion of cells with residual nucleoli in the metaphase and anaphase of mitosis. It is assumed that changes in the hormonal status of the cell (when explants were introduced into in vitro culture), the level of DNA methylation, and the degree of chromatin compaction could change the expression pattern of regulatory genes in the shoot apex (including the repression of transcription of key homeobox KNOX1 genes) and leaf reversion to the wild type. Moreover, the “epigenetic silence” induced by the in vitro conditions is quite stable and long-term: it has been observed for 19 years of clonal micropropagation using nutrient media without hormones, and it is also preserved after planting microplants in the greenhouse (ex vitro). Cultivated in vitro clones of Betula “dalecarlica,” contrasting in stability manifestations of the sign of dissected leaves, are a promising model for further studying the genetics of leaf morphogenesis and mechanisms of epigenetic variability.

Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus

The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.

Molecular cloning and expression characterization of flavonol synthase genes in peanut (Arachis hypogaea)

Flavonol is an important functional bioactive substance in peanut seeds, and plays important roles responding to abiotic stress. The flavonol content is closely related to the activity and regulation of gene expression patterns of flavonol synthase (FLS). In this study, eight FLS genes, AhFLSs were cloned and their expression characterization in different peanut organ and seedling under different abiotic stress were conducted. The results showed that the expressions levels of AhFLSs were differed in all assayed peanut organs and seedlings under abiotic stress treatments. Expression levels of AhFLS2, AhFLS3, AhFLS4, and AhFLS6 were higher than those of other AhFLSs. The flavonol contents of peanut organs and seedlings under different abiotic stress were also determined using high performance liquid chromatography (HPLC). Dried mature peanut seeds were the organ tissue with the highest flavonol content, and flavonol content increased with seed development. Under abiotic stress treatments, the types of flavonols induced differed among stress treatments. Correlation analysis results suggested that eight AhFLS genes may have different functions in peanut. Moreover, changes in the expression of the eight genes appear to has substrate preference. These results can lay the foundation for the study of improving nutritional value of peanut seed and resistance of peanut plant.

Production of plant bioactive triterpenoid saponins: from metabolites to genes and back

Saponins are specialized plant terpenoids derived from the mevalonic acid pathway. Triterpenoid saponin cores are decorated with sugar residues, conferring a highly amphipathic nature to these molecules, which show hypocholesterolemic, immunoadjuvant and anti-inflammatory activities, among others. Natural sources of bioactive saponins are relevant in light of the technical challenges of chemical synthesis of these compounds. Current supply of high quality, homogeneous and renewable plant material falls short of industrial demand. Research regarding molecular regulation of saponin metabolism has advanced considerably in recent years. Recent studies have focused on transcriptome analysis and identification of key transcription factors regulating gene expression patterns related to saponin biosynthesis. Biotechnological approaches to engineer saponin production in plants, organ and cell cultures, as well as development of heterologous expression systems, are being actively pursued as alternative sources of these high value plant terpenoids. It is expected that these efforts will impact industrial scale sustainable production systems in the coming years.

HEARTBREAK Controls Post-translational Modification of INDEHISCENT to Regulate Fruit Morphology in Capsella

SummaryMorphological variation is the basis of natural diversity and adaptation. For example, angiosperms (flowering plants) evolved during the Cretaceous period more than 100 mya and quickly colonized terrestrial habitats [1]. A major reason for their astonishing success was the formation of fruits, which exist in a myriad of different shapes and sizes [2]. Evolution of organ shape is fueled by variation in expression patterns of regulatory genes causing changes in anisotropic cell expansion and division patterns [3, 4, 5]. However, the molecular mechanisms that alter the polarity of growth to generate novel shapes are largely unknown. The heart-shaped fruits produced by members of the Capsella genus comprise an anatomical novelty, making it particularly well suited for studies on morphological diversification [6, 7, 8]. Here, we show that post-translational modification of regulatory proteins provides a critical step in organ-shape formation. Our data reveal that the SUMO protease, HEARTBREAK (HTB), from Capsella rubella controls the activity of the key regulator of fruit development, INDEHISCENT (CrIND in C. rubella), via de-SUMOylation. This post-translational modification initiates a transduction pathway required to ensure precisely localized auxin biosynthesis, thereby facilitating anisotropic cell expansion to ultimately form the heart-shaped Capsella fruit. Therefore, although variation in the expression of key regulatory genes is known to be a primary driver in morphological evolution, our work demonstrates how other processes—such as post-translational modification of one such regulator—affects organ morphology.

Evidence for Methylerythritol Pathway (MEP) Contributions to Zerumbone Biosynthesis as Revealed by Expression Analysis of Regulatory Genes and Metabolic Inhibitors Studies

Sesquiterpenoid Zerumbone, the principal secondary metabolite in Zingiber zerumbet Smith, has been identified as the putative molecule conferring resistance against soft-rot causative, Pythium myriotylum. Metabolic precursors for sesquiterpenoid biosynthesis namely, isopentenyl diphosphate (IPP) and DMAPP, are generated either from cytosolic mevalonic acid (MVA) and/or the plastidal methylerythritol phosphate (MEP) pathway. Evaluation of expression pattern of regulatory genes of MEP and MVA pathway following P. myriotylum infection revealed that while transcripts of MVA regulatory gene, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), did not show significant changes, biphasic expression pattern was observed for MEP pathway regulatory genes, viz., 1-deoxy-D-xylulose-5-phosphate reductase (DXR) and 1-deoxy-D-xylulose-5-phosphate synthase (DXS) as well for ZzTPS (terpene synthase) and Farnesyl phosphate synthase (FPS) compared with uninfected control. Contribution of the two pathways in zerumbone biosynthesis was evaluated in axenic tissue culture raised Z. zerumbet plantlets using MVA and MEP pathway specific inhibitors, mevinolin (MEV) and fosmidomycin (FOS) respectively. Results generated by regulatory gene and metabolite analysis are informative with respect to the role of plastidial IPP pool generated via MEP pathway in zerumbone biosynthesis and the possible redirection of flux in the event of metabolic perturbations mediated by chemical inhibitors.

Unraveling the role of H3K4 trimethylation and lncRNA HOTAIR in SATB1 and DUSP4-dependent survival of virulent Mycobacterium tuberculosis in macrophages

The modification of chromatin influences host transcriptional programs during bacterial infection, at times skewing the balance in favor of pathogen survival. To test the role of chromatin modifications during Mycobacterium tuberculosis infection, we analysed genome-wide deposition of H3K4me3 marks in macrophages infected with either avirulent M. tuberculosis H37Ra or virulent H37Rv, by chromatin immunoprecipitation, followed by sequencing. We validated differences in association of H3K4me3 at the loci of special AT-rich sequence binding protein 1 (SATB1) and dual specificity MAP kinase phosphatase 4 (DUSP4) between H37Rv and H37Ra-infected macrophages, and demonstrated their role in regulating bacterial survival in macrophages as well as the expression of chemokines. SATB1 repressed gp91phox (an NADPH oxidase subunit) thereby regulating reactive oxygen species (ROS) generation during infection. Long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in H37Ra-, but downregulated in H37Rv-infected macrophages. HOTAIR overexpression correlated with deposition of repressive H3K27me3 marks around the TSSs of DUSP4 and SATB1, suggesting that its downregulation favors the transcription of SATB1 and DUSP4. In summary, we have delineated histone modification- and lncRNA-dependent mechanisms regulating gene expression patterns facilitating survival of virulent M. tuberculosis. Our observations raise the possibility of harnessing histone-modifying enzymes to develop host-directed therapies for tuberculosis.

Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor for which structural information is available is WDR5, which interacts with MYC to facilitate its recruitment to chromatin. To explore whether disruption of the MYC-WDR5 interaction could potentially become a viable anticancer strategy, we developed a Burkitt's lymphoma system that allows replacement of wild-type MYC for mutants that are defective for WDR5 binding or all known nuclear MYC functions. Using this system, we show that WDR5 recruits MYC to chromatin to control the expression of genes linked to biomass accumulation. We further show that disrupting the MYC-WDR5 interaction within the context of an existing cancer promotes rapid and comprehensive tumor regression in vivo. These observations connect WDR5 to a core tumorigenic function of MYC and establish that, if a therapeutic window can be established, MYC-WDR5 inhibitors could be developed as anticancer agents.

DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome.

DNA methylation is an epigenetic modification essential for normal mammalian development. Initially associated with gene silencing, more diverse roles for DNA methylation in the regulation of gene expression patterns are increasingly being recognized. Some of these insights come from studying the function of genes that are mutated in human diseases characterized by abnormal DNA methylation landscapes. The first disorder to be associated with congenital defects in DNA methylation was Immunodeficiency, Centromeric instability, Facial anomalies syndrome (ICF). The hallmark of this syndrome is hypomethylation of pericentromeric satellite repeats, with mutations in four genes: DNMT3B, ZBTB24, CDCA7 and HELLS, being linked to the disease. Here, we discuss recent progress in understanding the molecular interactions between these genes and consider current evidence for how aberrant DNA methylation may contribute to the abnormal phenotype present in ICF syndrome patients.

The regulatory mechanism of Chryseobacterium sp. resistance mediated by montmorillonite upon cadmium stress

Cadmium (Cd) is a toxic heavy metal and its uptake by living organisms causes adverse effect, further resulting in cycle pollution of the biosphere. The specific regulatory mechanism between clays and microbes under Cd stress remains unclear. In this study, interface interactions among clays, microbes and Cd were confirmed. Comparative transcriptome was conducted to investigate how it regulated gene expression patterns of microbes (Chryseobacterium sp. WAL2), which exposed to a series of gradient concentrations of Cd (16, 32, 64 and 128 μg mL−1) for 12 d in the presence and absence of clay montmorillonite (Mt) (16 g L−1). Cd was highly enriched by the unique interface interactions between Mt and bacteria (67.6–82.1%), leading to a more hostile environment for bacterial cells. However, Mt ultimately enhanced bacterial resistance to Cd stress by stimulating the mechanism of bacterial resistance; namely: (i) Mt increased genes expression connected with ion transport, enhancing the uptake of Cd; (ii) Mt stimulated genes expression related to efflux pump and positively regulated cellular oxidative stress (e.g., glutathione) and Cd accumulation (e.g., cysteine) processes. Further, genes expression related to intracellular metabolic processes was enforced, which supplied a driving force and accelerated electron transfer; (iii) Mt improved genes expression involved in DNA replication and other biological processes (e.g., terpenoid backbone biosynthesis) to maintain bacterial vitality. Therefore, the study not only optimized a unique Cd resistance mechanism of Mt on Chryseobacterium sp., but also provided a novel insight for environmental mitigation of heavy metals from the perspective of molecular biology.

DNA methylation analysis of porcine mammary epithelial cells reveals differentially methylated loci associated with immune response against Escherichia coli challenge

BackgroundEpigenetic changes such as cytosine (CpG) DNA methylations regulate gene expression patterns in response to environmental cues including infections. Microbial infections induce DNA methylations that play a potential role in modulating host-immune response. In the present study, we sought to determine DNA methylation changes induced by the mastitis causing Escherichia coli (E. coli) in porcine mammary epithelial cells (PMEC). Two time points (3 h and 24 h) were selected based on specific transcriptomic changes during the early and late immune responses, respectively.ResultsDNA methylation analysis revealed 561 and 898 significant (P < 0.01) differentially methylated CpG sites at 3 h and 24 h after E. coli challenge in PMEC respectively. These CpG sites mapped to genes that have functional roles in innate and adaptive immune responses. Significantly, hypomethylated CpG sites were found in the promoter regions of immune response genes such as SDF4, SRXN1, CSF1 and CXCL14. The quantitative transcript estimation indicated higher expression associated with the DNA CpG methylation observed in these immune response genes. Further, E. coli challenge significantly reduced the expression levels of DNMT3a, a subtype of de novo DNA methylation enzyme, in PMEC indicating the probable reason for the hypomethylation observed in the immune response genes.ConclusionsOur study revealed E. coli infection induced DNA methylation loci in the porcine genome. The differentially methylated CpGs were identified in the regulatory regions of genes that play important role in immune response. These results will help to understand epigenetic mechanisms for immune regulation during coliform mastitis in pigs.

An Immune Gene Expression Signature Associated With Development of Human Hepatocellular Carcinoma Identifies Mice That Respond to Chemopreventive Agents

Cirrhosis and chronic inflammation precede development of hepatocellular carcinoma (HCC) in approximately 80% of cases. We investigated immune-related gene expression patterns in liver tissues surrounding early-stage HCCs and chemopreventive agents that might alter these patterns to prevent liver tumorigenesis. We analyzed gene expression profiles of nontumor liver tissues from 392 patients with early-stage HCC (training set, N= 167 and validation set, N= 225) and liver tissue from patients with cirrhosis without HCC (N= 216, controls) to identify changes in expression of genes that regulate the immune response that could contribute to hepatocarcinogenesis. We defined 172 genes as markers for this deregulated immune response, which we called the immune-mediated cancer field (ICF). We analyzed the expression data of liver tissues from 216 patients with cirrhosis without HCC and investigated the association between this gene expression signature and development of HCC and outcomes of patients (median follow-up, 10 years). Human liver tissues were also analyzed by histology. C57BL/6J mice were given a single injection of diethylnitrosamine (DEN) followed by weekly doses of carbon tetrachloride to induce liver fibrosis and tumorigenesis. Mice were then orally given the multiple tyrosine inhibitor nintedanib or vehicle (controls); liver tissues were collected and histology, transcriptome, and protein analyses were performed. We also analyzed transcriptomes of liver tissues collected from mice on a choline-deficient high-fat diet, which developed chronic liver inflammation and tumors, orally given aspirin and clopidogrel or the anti-inflammatory agent sulindac vs mice on a chow (control) diet. We found the ICF gene expression pattern in 50% of liver tissues from patients with cirrhosis without HCC and in 60% of nontumor liver tissues from patients with early-stage HCC. The liver tissues with the ICF gene expression pattern had 3 different features: increased numbers of effector T cells; increased expression of genes that suppress the immune response and activation of transforming growth factor β signaling; or expression of genes that promote inflammation and activation of interferon gamma signaling. Patients with cirrhosis and liver tissues with the immunosuppressive profile (10% of cases) had a higher risk of HCC (hazard ratio, 2.41; 95% confidence interval, 1.21-4.80). Mice with chemically induced fibrosis or diet-induced steatohepatitis given nintedanib or aspirin and clopidogrel down-regulated the ICF gene expression pattern in liver and developed fewer and smaller tumors than mice given vehicle. We identified an immune-related gene expression pattern in liver tissues of patients with early-stage HCC, called the ICF, that is associated with risk of HCC development in patients with cirrhosis. Administration of nintedanib or aspirin and clopidogrel to mice with chronic liver inflammation caused loss of this gene expression pattern and development of fewer and smaller liver tumors. Agents that alter immune regulatory gene expression patterns associated with carcinogenesis might be tested as chemopreventive agents in patients with cirrhosis.

Testicular miRNAs in relation to spermatogenesis, spermatogonial stem cells and cancer/testis genes

Abstract The process of spermatogenesis in human involves three organized biological processes, through which spermatogonia cells undergo mitosis, meiosis and finally differentiation into mature spermatozoa. Spermatogenesis requires a specifically regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators that have been reported to be involved in so many cellular processes including spermatogenesis, in which microRNAs are expressed in a stage-specific manner. Specific microRNAs are involved in the process of spermatogenesis and they have been identified to regulate and renew spermatogonia stem cell as well as been implicated in cancer biology regarding their effect in regulation of some of the cancer/testis genes.

Diabetic kidney disease: A systematic review on the role of epigenetics as diagnostic and prognostic marker.

Diabetic kidney disease is one of the most serious microvascular complications and among the leading causes of end stage renal disease. Persistently increasing albuminuria has been considered to be the central hallmark of nephropathy. However, albuminuria can indicate kidney damage for clinicians; it is not a specific biomarker for prediction of diabetic kidney disease prior to the onset of this devastating complication, and in fact all individuals with microalbuminuria do not progress to overt nephropathy. Controlled glycemia is unable to prevent nephropathy in all diabetic individuals indicating the role of other factors in progression of diabetic kidney disease. There are numerous cellular and molecular defects persisting prior to appearance of clinical symptoms. So, there is an urgent need to look for easy, novel, and accurate way to detect diabetic kidney disease prior to its beginning or at the infancy stage so that its progression can be slowed or arrested. It is now accepted that initiation and progression of diabetic kidney disease are a result of complex interactions between genetic and environmental factors. Environmental signals can alter the intracellular pathways by chromatin modifiers and regulate gene expression patterns leading to diabetes and its complications. In the present review, we have discussed a possible link between aberrant DNA methylation and altered gene expression in diabetic kidney disease. Drugs targeting to reverse epigenetic alteration can retard or stop the development of this devastating disease, just by breaking the chain of events occurring prior to the development of this microvascular complication in patients with diabetes.

Enteropathogens: Tuning Their Gene Expression for Hassle-Free Survival.

Enteropathogenic bacteria have been the cause of the majority of foodborne illnesses. Much of the research has been focused on elucidating the mechanisms by which these pathogens evade the host immune system. One of the ways in which they achieve the successful establishment of a niche in the gut microenvironment and survive is by a chain of elegantly regulated gene expression patterns. Studies have shown that this process is very elaborate and is also regulated by several factors. Pathogens like, enteropathogenic Escherichia coli (EPEC), Salmonella Typhimurium, Shigella flexneri, Yersinia sp. have been seen to employ various regulated gene expression strategies. These include toxin-antitoxin systems, quorum sensing systems, expression controlled by nucleoid-associated proteins (NAPs), several regulons and operons specific to these pathogens. In the following review, we have tried to discuss the common gene regulatory systems of enteropathogenic bacteria as well as pathogen-specific regulatory mechanisms.