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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

4.3K
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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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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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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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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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.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Related Experiment Video

Updated: Jun 28, 2025

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

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Comprehensive genomic features indicative for Notch responsiveness.

Benedetto Daniele Giaimo1, Tobias Friedrich1,2, Francesca Ferrante1

  • 1Institute of Biochemistry, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.

Nucleic Acids Research
|April 22, 2024
PubMed
Summary
This summary is machine-generated.

Notch signaling relies on transcription factor RBPJ. Dynamic RBPJ binding at enhancers, not static promoter binding, predicts gene responsiveness, aiding in understanding Notch pathway activity.

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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cell Signaling

Background:

  • Transcription factor RBPJ is central to Notch signaling, forming complexes with NICD.
  • Notch target gene expression varies dynamically with cell type and signaling state.
  • RBPJ protein levels are generally constant, contrasting with dynamic gene expression.

Purpose of the Study:

  • To investigate genome-wide RBPJ binding dynamics in response to Notch signaling.
  • To identify features distinguishing static versus dynamic RBPJ binding sites.
  • To predict Notch responsiveness based on RBPJ binding characteristics.

Main Methods:

  • Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map RBPJ occupancy.
  • Analysis of chromatin state, binding strength, and genomic location (enhancer vs. promoter).
  • Machine learning algorithms to predict gene responsiveness.

Main Results:

  • Only a subset of RBPJ sites exhibit dynamic binding in response to Notch signaling.
  • Dynamic RBPJ sites are predominantly distal (enhancers), while static sites are proximal (promoters).
  • Gene responsiveness strongly correlates with dynamic RBPJ binding at distal sites.

Conclusions:

  • Dynamic RBPJ binding at enhancers is a key determinant of Notch responsiveness.
  • Binding strength and enhancer positioning are crucial indicators of Notch pathway activity.
  • A machine learning model can reliably predict Notch responsiveness across different cellular contexts.