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Demethylase activity is directed by histone acetylation
1Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ H3G 1Y6, Canada.
The Journal of Biological Chemistry
|August 29, 2001
Summary
This study reveals that DNA methylation patterns in somatic cells are actively shaped by a demethylase, not just inherited. Histone acetylation guides this demethylase, suggesting a dynamic balance maintains gene methylation states.
Area of Science:
- Epigenetics
- Molecular Biology
- Genomics
Background:
- Mammalian genomes exhibit bimodal DNA methylation: hypermethylated inactive chromatin and hypomethylated active chromatin.
- This pattern is traditionally thought to be established during development and maintained by DNA methyltransferase 1 (DNMT1).
- Histone acetylation states are believed to direct DNA methylation patterns.
Purpose of the Study:
- To investigate the mechanisms shaping DNA methylation patterns in somatic cells.
- To challenge the prevailing model of methylation maintenance solely by inheritance.
- To explore the role of demethylation in establishing methylation patterns.
Main Methods:
- Utilized a transient transfection model in somatic cells.
- Assessed the influence of histone acetylation states on DNA methylation.
- Investigated the activity of DNA demethylase in shaping methylation patterns.
Main Results:
- Demonstrated the involvement of an active demethylase in shaping DNA methylation patterns.
- Showed that demethylase activity is directed by histone acetylation states.
- Identified histone acetylation as a determinant of methylation patterns, contrary to established models.
Conclusions:
- Proposed a new model where DNA methylation patterns are maintained by a dynamic balance of methylation and demethylation.
- Highlighted the crucial role of local histone acetylation states in this dynamic process.
- Provided a mechanism explaining why active genes remain hypomethylated.