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Characterization of open chromatin sensitive to actin polymerization and identification of core-binding factor

Yaxin Li1, Kangjing Li1, Fumihiko Nakamura1

  • 1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Cytoskeleton (Hoboken, N.J.)
|September 6, 2024
PubMed

Insights

Cellular mechanotransduction, crucial for biological responses, is linked to diseases. This study reveals how actin dynamics impact chromatin and gene expression, identifying a key protein in this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Mechanotransduction orchestrates diverse cellular functions, including gene expression and migration.
  • Actin cytoskeleton remodeling is central to mechanical signal transmission and cellular responses.
  • Dysregulated mechanotransduction is implicated in diseases like cancer and cardiovascular conditions.

Purpose of the Study:

  • To investigate the interplay between cellular mechanosensing, chromatin architecture, and nucleocytoplasmic transport.
  • To identify proteins involved in mechanosensitive nucleocytoplasmic shuttling.
  • To elucidate how actin polymerization dynamics influence chromatin organization and gene expression.

Main Methods:

  • Utilized the dithiobis(succinimidyl propionate) (DSP)-micrococcal nuclease (MNase) proteogenomics approach.
  • Examined alterations in open chromatin following actin filament depolymerization.
  • Investigated protein localization and nucleocytoplasmic shuttling.

Main Results:

  • Depolymerization of actin filaments using latrunculin B (Lat B) for 30 minutes significantly altered open chromatin structure.
  • Identified core-binding factor subunit beta as a novel mechanosensitive nucleocytoplasmic shuttling protein.
  • Demonstrated a direct link between actin dynamics, chromatin accessibility, and gene expression regulation.

Conclusions:

  • Actin cytoskeleton dynamics play a critical role in regulating chromatin accessibility and gene expression.
  • Core-binding factor subunit beta is a key mediator of mechanosensitive nucleocytoplasmic transport.
  • The DSP-MNase proteogenomics method is effective for studying mechanotransduction and its impact on the genome.
Keywords:
CBFBactinchromatincytoskeletonmechanotransduction

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