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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Related Experiment Video

Updated: Oct 22, 2025

Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
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Ras isoform-specific expression, chromatin accessibility, and signaling.

Ruth Nussinov1,2, Mingzhen Zhang1, Ryan Maloney1

  • 1Computational Structural Biology Section Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research in the Laboratory of Cancer Immunometabolism National Cancer Institute, 1050 Boyles St, Frederick, MD 21702 USA.

Biophysical Reviews
|September 1, 2021
PubMed
Summary
This summary is machine-generated.

Epigenetics and chromatin accessibility significantly influence Ras isoform expression across cell types. Understanding gene regulation requires examining how chromatin density controls access to DNA for gene expression.

Keywords:
Gene accessibilityHRASInhibitorK-RAS4AK-RAS4BKRASNRASSignaling

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biophysics

Background:

  • Ras isoforms' membrane anchorage and nanocluster formation are well-studied.
  • The role of epigenetics and chromatin accessibility in Ras isoform expression remains largely unexplored.
  • Ras isoforms are differentiated by their C-terminal hypervariable region (HVR), crucial for transport, regulation, and membrane anchoring.

Purpose of the Study:

  • To review Ras isoform-specific activities at the plasma membrane from a structural dynamic perspective.
  • To propose epigenetics and chromatin accessibility as key determinants of Ras isoform expression.
  • To integrate principles from physics and chemistry to understand biomolecular organization and functional specificity.

Main Methods:

  • Literature review focusing on structural dynamics of Ras isoforms.
  • Analysis of biomolecular organization in different cellular environments.
  • Conceptual framework linking chromatin density and accessibility to gene expression.

Main Results:

  • Ras isoform expression is likely controlled by chromatin density and physical compaction, regulating access to DNA.
  • Tissue-specific gene expression patterns can be partly explained by chromatin organization and accessibility.
  • Chromatin accessibility is a critical factor determining the expression of various genes, including drug resistance genes.

Conclusions:

  • Chromatin accessibility is a major, yet understudied, factor in regulating Ras isoform-specific expression.
  • Physical principles of biomolecular organization are essential for understanding functional specificity.
  • The proposed framework highlights the interplay between epigenetics, chromatin structure, and gene expression regulation.