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Updated: Apr 13, 2026

A G-quadruplex DNA-affinity Approach for Purification of Enzymatically Active G4 Resolvase1
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VGLL4-driven TEAD4 multimerization orchestrates DNA binding and YAP recruitment.

Zhiyun Ren1,2,3, Yilin Zhao1, Wentao Yu2

  • 1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

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|April 11, 2026
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Summary
This summary is machine-generated.

The Hippo pathway

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biophysics

Background:

  • The Hippo pathway regulates organ size and tissue homeostasis.
  • TEAD transcription factors are key downstream effectors, interacting with cofactors like YAP/TAZ and VGLL proteins.
  • Understanding TEAD-DNA interactions is crucial for deciphering gene regulation.

Purpose of the Study:

  • To investigate the DNA binding dynamics of TEAD4.
  • To explore the role of TEAD4 multimerization in DNA binding and YAP recruitment.
  • To elucidate the stoichiometry-dependent effect of VGLL4 on TEAD4-YAP interactions.

Main Methods:

  • Fluorescence-combined optical tweezers to measure DNA binding kinetics.
  • Analysis of TEAD4 monomeric and multimeric DNA binding.
  • Investigating the influence of YAP and VGLL4 on TEAD4 multimerization and DNA binding.

Main Results:

  • Monomeric TEAD4 exhibits fast dissociation from DNA, while multimerization enhances DNA residence time and YAP recruitment.
  • Both YAP and VGLL4 promote TEAD4 multimerization, strengthening DNA binding and specificity.
  • VGLL4's Tondu domains show a stoichiometry-dependent effect on YAP recruitment, enhancing it at low ratios and inhibiting at high ratios.

Conclusions:

  • TEAD4 DNA binding is dynamic, with multimerization significantly altering its interaction with DNA.
  • VGLL4 acts as a crucial regulator of TEAD4-mediated YAP recruitment in a concentration-dependent manner.
  • This study reveals a novel molecular mechanism for VGLL4 in modulating Hippo pathway signaling.