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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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Structure of a Gene01:30

Structure of a Gene

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A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
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Author Spotlight: Evaluation of Protein-Condensate Dynamics in Live Human Cells
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Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.

Gregory Foran1, Ryan Douglas Hallam1, Marvel Megaly1

  • 1Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada.

Scientific Reports
|September 19, 2024
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Summary
This summary is machine-generated.

Notch1 intracellular domain (NICD) forms nuclear condensates, promoting gene expression. This novel mechanism involves phase separation to recruit transcription factors and activate target genes like MYC.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Gene Regulation

Background:

  • The Notch receptor is a key signaling protein mediating cell-cell communication.
  • Notch signaling regulates gene expression through the nuclear translocation of its intracellular domain (NICD).

Purpose of the Study:

  • To elucidate the mechanism by which Notch intracellular Domain (NICD) regulates gene expression.
  • To investigate the role of NICD in forming nuclear condensates and their impact on transcription.

Main Methods:

  • Immunohistochemistry
  • RNA in situ hybridization
  • Optogenetics
  • Super-resolution live imaging of transcription in human cells

Main Results:

  • Notch1 intracellular Domain (N1ICD) forms nuclear condensates via Phase Separation Coupled Percolation (PSCP).
  • These condensates recruit and enrich core transcriptional proteins, facilitating gene expression.
  • The intrinsically disordered transcriptional activation domain of N1ICD drives condensate formation.
  • Transcriptional condensate formation promotes Notch-mediated super enhancer-looping and MYC protooncogene expression.

Conclusions:

  • N1ICD forms transcriptional condensates that enhance gene expression by concentrating transcriptional machinery.
  • This study reveals a novel mechanism for Notch1 activity involving phase separation and condensate assembly at target gene loci.