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Related Experiment Videos

Histone acetyltransferase activity in rat hepatomas.

H H Grunicke1, Y Yamada, Y Natsumeda

  • 1Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.

Journal of Cancer Research and Clinical Oncology
|January 1, 1989
PubMed
Summary

Histone acetyltransferase activity is elevated in rat hepatomas, correlating with tumor growth rate. However, overall histone acetylation levels remain unchanged, suggesting compensatory changes in protein content within tumors.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Histone acetylation is a key epigenetic mechanism regulating gene expression.
  • Previous studies indicated differences in histone acetylation between normal liver and hepatomas.
  • Histone acetyltransferase (EC 2.3.1.48) plays a crucial role in this process.

Purpose of the Study:

  • To investigate histone acetyltransferase activity in normal rat liver and various rat hepatomas.
  • To correlate enzyme activity with tumor growth rates (slow, intermediate, rapid).
  • To examine the impact of tumor growth on histone acetylation patterns.

Main Methods:

  • Assaying histone acetyltransferase specific activity (nmol h-1 mg total protein-1) in liver and hepatoma tissues.
  • Analyzing acetyltransferase activity per milligram of histone.

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  • Performing electrophoretic analysis of [3H]acetate-labeled histones.
  • Quantifying the frequency distribution of acetylated histone H4 species.
  • Main Results:

    • Specific histone acetyltransferase activity was significantly higher in all hepatomas compared to normal liver.
    • Increased enzyme activity positively correlated with hepatoma proliferation rates.
    • No difference in acetyltransferase activity per milligram of histone was observed.
    • Elevated histone and DNA to total protein ratios in hepatomas explained the specific activity findings.
    • Histone acetylation patterns, including histone H4 species distribution, were similar in hepatomas and normal liver.
    • Slowly growing hepatomas showed near-normal histone protein and acetate labeling.

    Conclusions:

    • Elevated histone acetyltransferase specific activity in hepatomas is linked to increased proliferation.
    • Compensatory changes in protein composition, not altered acetylation extent, characterize hepatomas.
    • Histone acetylation patterns are largely preserved despite increased enzyme activity in tumors.