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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

Mechanism of transcriptional activation by the proto-oncogene Twist1

Kristian Bruun Laursen1, Esther Mielke, Philip Iannaccone

  • 1Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.

The Journal of Biological Chemistry
|September 26, 2007
PubMed

Insights

Mammalian Twist1 protein can activate gene transcription through heterodimeric complexes with E12. This study identifies a novel Twist1 transactivation domain crucial for this function, revealing new insights into Twist1

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Mammalian Twist1 is a key regulator in development and tumorigenesis.
  • Twist1 is primarily known for repressing transcription.
  • Previous studies suggested a transactivation role for Twist1 but lacked mechanistic details.

Purpose of the Study:

  • To elucidate the mechanism by which Twist1 can activate transcription.
  • To identify novel functional domains and residues of Twist1 involved in transactivation.
  • To characterize the interaction between Twist1 and E12 in transcriptional regulation.

Main Methods:

  • Investigated the formation of heterodimeric complexes between Twist1 and E12.
  • Identified and characterized a novel transactivation domain within Twist1.
  • Utilized site-directed mutagenesis to pinpoint essential residues in the WR domain.
  • Proposed an alpha-helical structure for the Twist1 transactivation domain.

Main Results:

  • Twist1 forms heterodimeric complexes with E12 that mediate E-box-dependent transcriptional activation.
  • A novel transactivation domain in Twist1 was identified, which coactivates with E12.
  • Three specific residues within the conserved WR domain of murine Twist1 are essential for its transactivating function.
  • Evidence suggests an alpha-helical structure for the Twist1 transactivation domain.

Conclusions:

  • Twist1 can function as a transcriptional activator through interaction with E12.
  • The WR domain of Twist1 harbors a novel transactivation domain critical for this activity.
  • Understanding Twist1's dual role in transcription (repression and activation) is crucial for development and cancer research.

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