Related Experiment Video

Updated: Jul 17, 2026

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events
10:59

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events

Published on: May 13, 2019

Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription

Yunsun Nam1, Piotr Sliz, Warren S Pear

  • 1Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|February 8, 2007
PubMed

Insights

Notch signaling requires dimeric transcription complexes on paired DNA sites for gene activation. This discovery clarifies Notch pathway sensitivity and aids in identifying target genes and developing new inhibitors.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Notch receptors regulate cell differentiation and are implicated in cancer.
  • Notch signaling involves interaction with the CSL transcription factor to control target gene expression.
  • Many Notch targets feature paired CSL-binding sites in a head-to-head configuration.

Purpose of the Study:

  • To elucidate the mechanism of Notch-induced transcription activation on promoters with paired CSL-binding sites.
  • To understand how paired binding sites contribute to Notch target gene sensitivity and regulation.
  • To provide a basis for improved identification of Notch target genes and development of novel inhibitors.

Main Methods:

  • Combination of structural biology techniques.
  • Application of molecular approaches to study protein-DNA interactions.
  • Analysis of Notch transcription complex formation on DNA promoters.

Main Results:

  • Cooperative formation of dimeric Notch transcription complexes is essential for activating transcription on paired CSL-binding sites.
  • This cooperative binding mechanism explains the sensitivity of Notch target genes to signal strength and developmental context.
  • Identified a key mechanistic step in Notch pathway regulation.

Conclusions:

  • Dimeric complex formation on paired sites is a critical requirement for Notch-mediated transcriptional activation.
  • Findings facilitate sensitive and reliable identification of Notch target genes.
  • Lays groundwork for developing targeted Notch pathway inhibitors for diseases like cancer.

More Related Videos

High-throughput Purification of Affinity-tagged Recombinant Proteins07:44

High-throughput Purification of Affinity-tagged Recombinant Proteins

Published on: August 26, 2012

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA07:05

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA

Published on: September 8, 2021

Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...