NANOG Assembles into Self-Limiting Aging Micelles That Drive a Sol-Gel Transition and Modulate DNA Dynamics

Area of Science:

• Biophysics
• Molecular Biology
• Stem Cell Biology

Background:

• Proteins and nucleic acids exhibit complex rheological properties essential for their biological functions.
• The transcription factor NANOG is crucial for maintaining embryonic stem cell pluripotency.

Purpose of the Study:

• To investigate the rheology of NANOG and its role in cellular function.
• To understand how NANOG's structure influences its rheological properties and interactions with DNA.

Main Methods:

• Molecular dynamics simulations
• Mass photometry
• Cryo-electron microscopy (cryo-EM)

Main Results:

• At high concentrations, NANOG forms macroscopic aging gels dependent on its intrinsically disordered domain.
• NANOG forms self-limiting micelles with exposed DNA-binding domains, unlike other intrinsically disordered proteins.
• These NANOG micelles stabilize DNA entanglements and modulate DNA dynamics.

Conclusions:

• NANOG may regulate gene expression by forming local gel-like environments that restrict genome dynamics.
• The aging of NANOG gels might introduce mechanical memory into gene regulatory networks.