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Correlation between butyrate-induced histone hyperacetylation turn-over and c-myc expression
Maria Rita Mariani1, Elisabetta M Carpaneto, Massimo Ulivi
1SS of Epigenetic, Department of Etiology and Epidemiology, National Cancer Research Institute, IST, Lgo Rosanna Benzi 10, 16132 Genoa, Italy.
The Journal of Steroid Biochemistry and Molecular Biology
|October 22, 2003
Summary
Sodium butyrate, a histone deacetylase inhibitor, was studied for its effect on c-myc gene expression. Researchers found a strong link between increased histone acetylation and the reactivation of c-myc gene expression in HeLa cells.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Transcriptionally active chromatin exhibits high histone acetylation, which enhances DNA accessibility for transcription factors.
- Histone acetyltransferases and deacetylases are gaining attention for their roles in gene regulation.
- Sodium butyrate is a known reversible inhibitor of histone deacetylase and affects numerous genes.
Purpose of the Study:
- To investigate the modulation of c-myc oncogene expression by sodium butyrate.
- To establish a correlation between c-myc expression reactivation and histone H4 acetylation levels.
Main Methods:
- HeLa cells were treated with sodium butyrate and then transferred to a butyrate-free medium.
- Quantitative analysis of histone acetylation levels and c-myc expression in different nucleosomal fragments.
- Detection of c-myc sequences in active and inactive chromatin fractions.
Main Results:
- A correlation was observed between the kinetics of c-myc expression reactivation and increased histone H4 acetylation.
- Both c-myc expression and histone acetylation showed a rebound effect and returned to control levels in butyrate-free medium.
- Quantitative analysis confirmed the enrichment of c-myc sequences in active chromatin fractions and decreased presence in inactive fractions.
Conclusions:
- There is an excellent correlation between histone hyperacetylation and the reactivation of the c-myc gene.
- Histone acetylation is a key epigenetic mechanism regulating c-myc oncogene expression.