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Functionally relevant histone-DNA interactions extend beyond the classically defined nucleosome core region

C Thiriet1, J J Hayes

  • 1Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.

The Journal of Biological Chemistry
|August 8, 1998
PubMed
Summary
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Core histones significantly reduce transcription factor binding affinity, even for DNA sites outside the nucleosome. This impacts understanding DNA accessibility in chromatin regulation.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Chromatin Structure

Background:

  • Nucleosomes, the basic units of DNA packaging, are formed by core histones.
  • The accessibility of DNA within chromatin is crucial for gene regulation.
  • Transcription factors bind to specific DNA sequences to control gene expression.

Purpose of the Study:

  • To investigate how core histones influence the binding of transcription factors to DNA elements located outside the canonical nucleosome core region.
  • To quantify the effect of nucleosome proximity on transcription factor binding affinity.

Main Methods:

  • Systematic variation of the distance between a positioned nucleosome and the DNA binding site for TFIIIA (5S-specific transcription factor).
  • Determination of the relative binding affinity of TFIIIA to its DNA element under varying nucleosome positions.

Related Experiment Videos

  • Utilizing quantitative biochemical assays to measure DNA-protein interactions.

    • Main Results:

    • Core histone-DNA interactions significantly attenuate TFIIIA binding affinity by 50-100 fold.
    • This attenuation occurs even when the TFIIIA binding site is well outside the classically defined nucleosome core region.
    • The proximity and interaction of core histones with DNA impact the accessibility for sequence-specific DNA-binding factors.

    Conclusions:

    • Core histones can restrict access of transcription factors to DNA elements beyond the immediate nucleosome structure.
    • The findings challenge assumptions that only DNA within the nucleosome core is significantly affected by histone interactions.
    • This has critical implications for models of gene regulation and the interpretation of DNA accessibility studies in chromatin.