scholarly journals CopR, a global regulator of transcription to maintain copper homeostasis in Pyrococcus furiosus

2020 ◽  
Author(s):  
Felix Grünberger ◽  
Robert Reichelt ◽  
Ingrid Waege ◽  
Verena Ned ◽  
Korbinian Bronner ◽  
...  
Keyword(s):  
Essential Role ◽  
Pyrococcus Furiosus ◽  
Copper Homeostasis ◽  
Negative Stain ◽  
Cellular Life ◽  
Transmission Electron ◽  
Genome Wide ◽  
Binding Data ◽  
Differential Gene

AbstractAlthough copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analysed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process.To this end, we employed biochemical and biophysical methods to characterise the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 μM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the complex regulatory network that enables Pyrococcus to respond to increased copper concentrations.

scholarly journals CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus

2021 ◽  
Vol 11 ◽  
Author(s):  
Felix Grünberger ◽  
Robert Reichelt ◽  
Ingrid Waege ◽  
Verena Ned ◽  
Korbinian Bronner ◽  
...  
Keyword(s):  
Essential Role ◽  
Pyrococcus Furiosus ◽  
Copper Homeostasis ◽  
Negative Stain ◽  
Cellular Life ◽  
Transmission Electron ◽  
Genome Wide ◽  
Binding Data ◽  
Differential Gene

Although copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analyzed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process. To this end, we employed biochemical and biophysical methods to characterize the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 μM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the regulatory network that enables Pyrococcus to respond to increased copper concentrations.

scholarly journals The Cardamine hirsuta genome offers insight into the evolution of morphological diversity

Nature Plants ◽  
2016 ◽  
Vol 2 (11) ◽  
Author(s):  
Xiangchao Gan ◽  
Angela Hay ◽  
Michiel Kwantes ◽  
Georg Haberer ◽  
Asis Hallab ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Human Genetics ◽  
Morphological Evolution ◽  
Morphological Diversity ◽  
Close Relative ◽  
Gene Duplications ◽  
Tandem Gene Duplication ◽  
Genome Wide ◽  
Differential Gene

Abstract Finding causal relationships between genotypic and phenotypic variation is a key focus of evolutionary biology, human genetics and plant breeding. To identify genome-wide patterns underlying trait diversity, we assembled a high-quality reference genome of Cardamine hirsuta, a close relative of the model plant Arabidopsis thaliana. We combined comparative genome and transcriptome analyses with the experimental tools available in C. hirsuta to investigate gene function and phenotypic diversification. Our findings highlight the prevalent role of transcription factors and tandem gene duplications in morphological evolution. We identified a specific role for the transcriptional regulators PLETHORA5/7 in shaping leaf diversity and link tandem gene duplication with differential gene expression in the explosive seed pod of C. hirsuta. Our work highlights the value of comparative approaches in genetically tractable species to understand the genetic basis for evolutionary change.

scholarly journals The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 974 ◽  
Author(s):  
Shantae M. Thornton ◽  
Varsha D. Samararatne ◽  
Joseph G. Skeate ◽  
Christopher Buser ◽  
Kim P. Lühen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Processing ◽  
Viral Antigen ◽  
Essential Role ◽  
Critical Role ◽  
The Body ◽  
Birbeck Granules ◽  
Transmission Electron ◽  
Antigen Presenting

Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.

scholarly journals Analysis of the Placental Tissue Transcriptome of Normal and Preeclampsia Complicated Pregnancies

Acta Naturae ◽  
2014 ◽  
Vol 6 (2) ◽  
pp. 71-83 ◽  
Author(s):  
E. A. Trifonova ◽  
T. V. Gabidulina ◽  
N. I. Ershov ◽  
V. N. Serebrova ◽  
A. Yu. Vorozhishcheva ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Placental Tissue ◽  
Immunological Tolerance ◽  
Leading Role ◽  
New Genes ◽  
Genome Wide ◽  
Differential Gene

Preeclampsia is one of the most severe gestational complications which is one of the leading causes of maternal and perinatal morbidity and mortality. A growth in the incidence of severe and combined forms of the pathology has been observed in recent years. According to modern concepts, inadequate cytotrophoblast invasion into the spiral arteries of the uterus and development of the ischemia-reperfusion syndrome in the placental tissue play the leading role in the development of preeclampsia, which is characterized by multipleorgan failure. In this regard, our work was aimed at studying the patterns of placental tissue transcriptome that are specific to females with PE and with physiological pregnancy, as well as identifying the potential promising biomarkers and molecular mechanisms of this pathology. We have identified 63 genes whose expression proved to differ significantly in the placental tissue of females with PE and with physiological pregnancy. A cluster of differentially expressed genes (DEG) whose expression level is increased in patients with preeclampsia includes not only the known candidate genes that have been identified in many other genome-wide studies (e.g., LEP, BHLHB2, SIGLEC6, RDH13, BCL6), but also new genes (ANKRD37, SYDE1, CYBA, ITGB2, etc.), which can be considered as new biological markers of preeclampsia and are of further interest. The results of a functional annotation of DEG show that the development of preeclampsia may be related to a stress response, immune processes, the regulation of cell-cell interactions, intracellular signaling cascades, etc. In addition, the features of the differential gene expression depending on preeclampsia severity were revealed. We have found evidence of the important role of the molecular mechanisms responsible for the failure of immunological tolerance and initiation of the pro-inflammatory cascade in the development of severe preeclampsia. The results obtained elaborate the concept of the pathophysiology of preeclampsia and contain the information necessary to work out measures for targeted therapy of this disease.

scholarly journals Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription

2010 ◽  
Vol 39 (8) ◽  
pp. 3116-3127 ◽  
Author(s):  
Yannick-Noël Anno ◽  
Evelyne Myslinski ◽  
Richard Patryk Ngondo-Mbongo ◽  
Alain Krol ◽  
Olivier Poch ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Essential Role ◽  
Bidirectional Transcription ◽  
Genome Wide

scholarly journals Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney

2020 ◽  
Vol 31 (11) ◽  
pp. 2543-2558 ◽  
Author(s):  
Sierra S. Marable ◽  
Eunah Chung ◽  
Joo-Seop Park
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Major Function ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Developing Kidney ◽  
Differential Gene ◽  
Direct Target ◽  
Novel Model

BackgroundHepatocyte NF 4α (Hnf4a) is a major regulator of renal proximal tubule (PT) development. In humans, a mutation in HNF4A impairs PT functions and is associated with Fanconi renotubular syndrome (FRTS). In mice, mosaic deletion of Hnf4a in the developing kidney reduces the population of PT cells, leading to FRTS-like symptoms. The molecular mechanisms underlying the role of Hnf4a in PT development remain unclear.MethodsThe gene deletion tool Osr2Cre removed Hnf4a in developing nephrons in mice, generating a novel model for FRTS. Immunofluorescence analysis characterized the mutant phenotype, and lineage analysis tested whether Cadherin-6 (Cdh6)–expressing cells are PT progenitors. Genome-wide mapping of Hnf4a binding sites and differential gene analysis of Hnf4a mutant kidneys identified direct target genes of Hnf4a.ResultsDeletion of Hnf4a with Osr2Cre led to the complete loss of mature PT cells, lethal to the Hnf4a mutant mice. Cdh6high, lotus tetragonolobus lectin-low (LTLlow) cells serve as PT progenitors and demonstrate higher proliferation than Cdh6low, LTLhigh differentiated PT cells. Additionally, Hnf4a is required for PT progenitors to differentiate into mature PT cells. Genomic analyses revealed that Hnf4a directly regulates the expression of genes involved in transmembrane transport and metabolism.ConclusionsHnf4a promotes the differentiation of PT progenitors into mature PT cells by regulating the expression of genes associated with reabsorption, the major function of PT cells.

scholarly journals Genome-Wide miRNA Seeds Prediction in Archaea

Archaea ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Shengqin Wang ◽  
Yuming Xu ◽  
Zuhong Lu
Keyword(s):  
Noncoding Rna ◽  
Statistical Significance ◽  
Mature Mirnas ◽  
Phylogenetic Information ◽  
Mirna Genes ◽  
Cellular Life ◽  
Genome Wide ◽  
Genomic Scale ◽  
Study Support

Growing evidence indicates that miRNA genes exist in the archaeal genome, though the functional role of such noncoding RNA remains unclear. Here, we integrated the phylogenetic information of available archaeal genomes to predict miRNA seeds (typically defined as the 2–8 nucleotides of mature miRNAs) on the genomic scale. Finally, we found 2649 candidate seeds with significant conservation signal. Eleven of 29 unique seeds from previous study support our result (Pvalue<0.01), which demonstrates that the pipeline is suitable to predict experimentally detectable miRNA seeds. The statistical significance of the overlap between the detected archaeal seeds and known eukaryotic seeds shows that the miRNA may evolve before the divergence of these two domains of cellular life. In addition, miRNA targets are enriched for genes involved in transcriptional regulation, which is consistent with the situation in eukaryote. Our research will enhance the regulatory network analysis in Archaea.

On Future Directions in Pathology

1982 ◽  
Vol 40 ◽  
pp. 274-277
Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Clinical Pathology ◽  
Future Directions ◽  
Diagnostic Pathology ◽  
The Past ◽  
Transmission Electron ◽  
Organ Systems ◽  
The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

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