scholarly journals Genomic Competition for Noise Reduction Shaped Evolutionary Landscape of Mir-4673

2019 ◽  
Author(s):  
Ramin M Farahani ◽  
Saba Rezaei-Lotfi ◽  
Neil Hunter
Keyword(s):  
Notch 1 ◽  
Transcriptional Noise ◽  
Evolutionary Trajectory ◽  
Genomic Platform ◽  
Selective Forces ◽  
Latent Potential ◽  
Genomic Element ◽  
Noise In Gene Expression ◽  
Noise Buffering ◽  
Transcriptional Landscape

AbstractThe genomic platform that informs evolution of microRNA cascades remains unknown. Here we capitalized on the recent evolutionary trajectory of hominin-specific miRNA-4673 (Dokumcu et al., 2018) encoded in intron 4 of notch-1 to uncover the identity of one such precursor genomic element and the selective forces acting upon it. The miRNA targets genes that regulate Wnt/β-catenin signalling cascade. Primary sequence of the microRNA and its target region in Wnt modulating genes evolved from homologous signatures mapped to homotypic cis-clusters recognised by TCF3/4 and TFAP2A/B/C families. Integration of homologous TFAP2A/B/C cis-clusters (short range inhibitor of β-catenin (Li and Dashwood, 2004)) into the transcriptional landscape of Wnt cascade genes can reduce noise in gene expression (Blake et al., 2003). Probabilistic adoption of miRNA secondary structure by one such cis-signature in notch-1 reflected selection for superhelical curvature symmetry of precursor DNA to localize a nucleosome that overlapped the latter cis-cluster. By replicating the cis-cluster signature, non-random interactions of the miRNA with key Wnt modulator genes expanded the transcriptional noise buffering capacity via a coherent feed-forward loop mechanism (Hornstein and Shomron, 2006). In consequence, an autonomous transcriptional noise dampener (the cis-cluster/nucleosome) evolved into a post-transcriptional one (the miRNA). The findings suggest a latent potential for remodelling of transcriptional landscape by miRNAs that capitalize on non-random distribution of genomic cis-signatures.

scholarly journals Pathway dynamics can delineate the sources of transcriptional noise in gene expression

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lucy Ham ◽  
Marcel Jackson ◽  
Michael Stumpf
Keyword(s):  
Intrinsic Noise ◽  
Stochastic Simulations ◽  
Transcriptional Noise ◽  
Extrinsic Noise ◽  
Cellular Processes ◽  
Dual Reporter ◽  
Extensive Cell ◽  
Noise In Gene Expression ◽  
Cell Expression ◽  
Cell To Cell Variability

Single-cell expression profiling opens up new vistas on cellular processes. Extensive cell-to-cell variability at the transcriptomic and proteomic level has been one of the stand-out observations. Because most experimental analyses are destructive we only have access to snapshot data of cellular states. This loss of temporal information presents significant challenges for inferring dynamics, as well as causes of cell-to-cell variability. In particular, we typically cannot separate dynamic variability from within cells ('intrinsic noise') from variability across the population ('extrinsic noise'). Here we make this non-identifiability mathematically precise, allowing us to identify new experimental set-ups that can assist in resolving this non-identifiability. We show that multiple generic reporters from the same biochemical pathways (e.g. mRNA and protein) can infer magnitudes of intrinsic and extrinsic transcriptional noise, identifying sources of heterogeneity. Stochastic simulations support our theory, and demonstrate that 'pathway-reporters' compare favourably to the well-known, but often difficult to implement, dual-reporter method.

TNFα blockade inhibits T cell cycling by NOTCH-1 signaling

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
L Werner ◽  
D Paclik ◽  
U Berndt ◽  
B Wiedenmann ◽  
A Sturm
Keyword(s):  
T Cell ◽  
Notch 1 ◽  
Cell Cycling

Expression of Notch 1,HIF-1α in human renal carcinoma and its relation with clinical tumor staging

2009 ◽  
Vol 29 (8) ◽  
pp. 970-971
Author(s):  
Run-lin YAN ◽  
Lin-hui WANG ◽  
Ying-hao SUN
Keyword(s):  
Renal Carcinoma ◽  
Tumor Staging ◽  
Notch 1 ◽  
Human Renal Carcinoma

Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway.

2020 ◽  
Vol 20 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mohd Saeed ◽  
Irfan Ahmad ◽  
Irfan A. Ansari
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Mtt Assay ◽  
Annexin V ◽  
Notch Signaling Pathway ◽  
Phase Cell ◽  
Ros Generation ◽  
Notch 1

Background: Recently Notch signaling pathway has gained attention as a potential therapeutic target for chemotherapeutic intervention. However, the efficacy of previously known Notch inhibitors in colon cancer is still unclear. The purpose of this study was to investigate the effect of andrographolide on aberrantly activated Notch signaling in SW-480 cells in vitro. Methods: The cytostatic potential of andrographolide on SW-480 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, morphology assessment and colony formation assay. The apoptotic activity was evaluated by FITC Annexin V assay, 4′,6-diamidino-2-phenylindole (DAPI), Hoechst, Rhodamine 123 and Mito Tracker CMXRos staining. Scratch assay for migratory potential assessment. 7’-Dichlorodihydrofluorescein Diacetate (DCFH-DA) staining was used to evaluate the Reactive Oxygen Species (ROS) generation. Relative mRNA expression of Bax, Bcl2, NOTCH 1 and JAGGED 1 was estimated by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Cell cycle phase distribution was evaluated Annexin V-FITC/PI staining. Results: MTT assay demonstrated dose and time dependent cytoxicity of andrographolide on SW-480 cells. It also inhibited the migratory and colony forming potential of SW-480 cells. Furthermore, andrographolide also showed disruption of mitochondrial membrane potential and induced apoptosis through nuclear condensation. Flow cytometric evaluation showed andrographolide enhanced early and late apoptotic cells and induced upregulation of proapoptotic (Bax and Bad) and downregulation of antiapoptotic Bcl2 in treated SW-480 cells. Andrographolide augmented intracellular ROS generation and induced G0/G1 phase cell cycle arrest in colon cancer SW480 cells. Furthermore, andrographolide repressed the Notch signaling by decreasing the expression of NOTCH 1 and JAGGED 1. Conclusion: Our findings suggested that andrographolide constraint the growth of SW-480 cells through the inhibition of Notch signaling pathway.

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