scholarly journals The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway

2002 ◽  
Vol 16 (15) ◽  
pp. 1977-1989 ◽  
Author(s):  
Y. Liang
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Functional Interaction

scholarly journals Retinal Genomic Fabrics Remodeling after Optic Nerve Injury

2021 ◽  
Author(s):  
Pedro Henrique Victorino ◽  
Camila Marra ◽  
Dumitru Andrei Iacobas ◽  
Sanda Iacobas ◽  
David C Spray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Complement Cascade ◽  
Gene Expressions ◽  
Nerve Crush ◽  
Individual Gene

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

scholarly journals The Notch Pathway Intermediate HES-1 Silences CD4 Gene Expression

1998 ◽  
Vol 18 (12) ◽  
pp. 7166-7175 ◽  
Author(s):  
Han K. Kim ◽  
Gerald Siu
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Transcriptional Control ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Thymic Development ◽  
Enhancer Function ◽  
Enhancer Of Split

ABSTRACT We have previously identified a transcriptional silencer that is critical for proper expression of the CD4 gene during T-cell development. Here we report that the Hairy/Enhancer of Split homologue HES-1, a transcription factor in the lin12/Notch signaling pathway, binds to an important functional site in the CD4 silencer. Overexpression of HES-1 leads to the silencer site-dependent repression of CD4 promoter and enhancer function as well as the downregulation of endogenous CD4 expression in CD4+ CD8−TH cells. Interestingly, overexpression of an activated form of Notch1 (NotchIC) leads to the repression of CD4 promoter and enhancer function both in the presence and absence of the silencer. NotchIC-mediated CD4 silencer function is not affected by the deletion of the HES-1-binding site, indicating that multiple factors binding to CD4 transcriptional control elements are responsive to signaling from this pathway, including other silencer-binding factors. Taken together, these data are consistent with the hypothesis that the lin12/Notch signaling pathway is important in thymic development and provide a molecular mechanism via the control of CD4 gene expression in which the lin12/Notch pathway affects T-cell developmental fate.

scholarly journals Retinal Genomic Fabric Remodeling after Optic Nerve Injury

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 403
Author(s):  
Pedro Henrique Victorino ◽  
Camila Marra ◽  
Dumitru Andrei Iacobas ◽  
Sanda Iacobas ◽  
David C. Spray ◽  
...  
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Complement Cascade ◽  
Gene Expressions ◽  
Nerve Crush ◽  
Individual Gene

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers three independent characteristics for the expression of each gene: level, variability, and correlation with each other gene. Thus, the 17,657 quantified genes in our study generated a total of 155,911,310 values to analyze. This represents 8830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI). We observed a higher relative expression variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted protein–protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among upregulated genes. Enrichment analysis showed that complement cascade and Notch signaling pathway, as well as oxidative stress and kit receptor pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pairwise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in complement cascade and Notch signaling pathway. This deep bioinformatic study provided novel insights beyond the regulation of individual gene expression and disclosed changes in the control of expression of complement cascade and Notch signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

scholarly journals Pathogenesis of Barrett's esophagus: Bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells

Surgery ◽  
2009 ◽  
Vol 146 (4) ◽  
pp. 714-722 ◽  
Author(s):  
David J. Morrow ◽  
Nelly E. Avissar ◽  
Liana Toia ◽  
Eileen M. Redmond ◽  
Thomas J. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Bile Acids ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Notch Signaling Pathway

Gene expression analysis of Notch signaling pathway receptors in colon cancer stem cells.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 29-29
Author(s):  
Ioannis Papasotiriou ◽  
Panagiotis Apostolou ◽  
Maria Toloudi ◽  
Marina Chatziioannou ◽  
Eleni Ioannou
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Expression Analysis ◽  
Protein Level ◽  
Gene Expression Analysis ◽  
Notch Signaling Pathway ◽  
Notch 1 ◽  
Notch 3 ◽  
Notch Receptors

29 Background: The Notch signaling pathway is not only involved in cell differentiation, but also in carcinogenesis. Four different receptors are included in this pathway (Notch-1, Notch-2, Notch-3, and Notch-4) and each is encoded by a different gene. Recent data suggest that the activation of Notch-1 induces epithelial to mesenchymal transition (EMT) consistent with cancer stem cell (CSC) phenotype. It raises therefore the question of whether there is an interaction between the receptors. The present study aims to find out the gene expression patterns of Notch receptors in Colon CSCs, under the suppression of Notch-1. Methods: The experiments were performed in Colon CSCs provided by CELPOGEN. The stemness of these cells was tested both in gene and protein level with qPCR and flow cytometry assays for the stemness markers Oct4-CD44. The gene suppressed with RNAi assays and the knockdown was evaluated with molecular biology methods. The gene expression analysis was performed after RT-qPCR assays, by using the comparative Ct method (ΔΔCt) for the calculation of relative quantitation. Results: The Colon CSCs expressed Oct4-CD44 both in gene and protein level, indicating the stemness status. The knockdown of Notch-1 up to 75%, led to a reduction of gene expression in Notch-2 and Notch-3 receptors, while no significant difference was observed in Notch-4. The Notch-2 expression was decreased up to 90% while that of Notch-3 was at the same level with Notch-1. Conclusions: This research study attempts to find out any possible correlation between the Notch receptors in Colon CSCS. The experimental data indicate that Notch-1 interacts with Notch-2 and Notch-3 by affecting heavily their gene expression. It is therefore necessary to study if the other receptors are capable for EMT and then to find out which factors are involved. Further studies to a greater range of samples need to be performed, in order to use these data at clinical level.

scholarly journals KLF4 gene expression is inhibited by the notch signaling pathway that controls goblet cell differentiation in mouse gastrointestinal tract

2009 ◽  
Vol 296 (3) ◽  
pp. G490-G498 ◽  
Author(s):  
Hai Zheng ◽  
D. Mark Pritchard ◽  
Xiangdong Yang ◽  
Elaine Bennett ◽  
Gang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Cell Differentiation ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Goblet Cell ◽  
Promoter Activity ◽  
Notch Signaling Pathway ◽  
Goblet Cell Differentiation ◽  
Responsive Element

In Kruppel-like factor (KLF)-4-deficient mice, colonic goblet cell numbers are significantly reduced. Goblet cell development is regulated by the Notch signaling pathway. The aim of this study was to examine whether Notch represses KLF4 expression to regulate goblet cell differentiation. We first detected that KLF4 gene expression was upregulated in a human progastrin-overexpressing mouse model where goblet cell hyperplasia has been observed. We then found that mice treated with a γ-secretase inhibitor (compound E, 10 μmol/kg) for 24 h, which inhibits the Notch signaling pathway, had significantly increased KLF4 mRNA levels in small intestine and colon, accompanied by an increased number of KLF4-expressing cells at the bottom of crypts in small intestine and colon. In a colon cancer cell line (HCT116 cells), KLF4 promoter activity was inhibited by a constitutively active form of Notch1 (ICN1) by transient cotransfection assays. This inhibition was significantly compromised by a dominant-negative RBPjk, a repressive mediator of the Notch signaling pathway. An ICN1-responsive element was then mapped in the human KLF4 promoter between −151 and −122 nucleotides upstream of the transcriptional start site. It was also found that an intact ICN1-responsive element is required for ICN1 to inhibit KLF4 promoter activity by transient cotransfection assays. Our findings thus reveal a possible mechanism by which KLF4 is inhibited by Notch, which controls goblet cell differentiation in mouse gastrointestinal tract.

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