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Published on: August 1, 2017
A novel mammalian flavin-dependent histone demethylase
Aristotele Karytinos1, Federico Forneris, Antonella Profumo
1Dipartimento di Genetica e Microbiologia, Università di Pavia, Via Ferrata 1, 27100 Pavia, Italy.
The Journal of Biological Chemistry
|May 2, 2009
Summary
Researchers discovered a new enzyme, lysine-specific demethylase 2 (LSD2), which removes epigenetic marks from histone H3. This flavin-dependent histone demethylase is similar to LSD1 but functions in distinct chromatin-remodeling complexes.
Area of Science:
- Epigenetics
- Molecular Biology
- Enzymology
Background:
- Histone methylation is a key epigenetic mark regulating gene expression.
- Lysine-specific demethylase 1 (LSD1) dynamically controls lysine methylation via flavin-dependent amine oxidation.
- Mammalian genomes contain a gene homologous to LSD1, named AOF1.
Purpose of the Study:
- To identify and characterize the protein encoded by the AOF1 gene.
- To determine if AOF1 encodes a novel histone demethylase.
- To compare the properties of this new enzyme with LSD1.
Main Methods:
- Database analysis to identify homologous genes.
- Biochemical assays to characterize enzyme activity.
- Inhibition studies using tranylcypromine.
- Analysis of protein complex formation with CoREST.
- Structural motif analysis (zinc finger).
Main Results:
- The AOF1 gene encodes a second mammalian flavin-dependent histone demethylase, named LSD2.
- LSD2 is strictly specific for mono- and dimethylated Lys4 of histone H3.
- LSD2 recognizes a long stretch of the H3 N-terminal tail and senses other epigenetic marks.
- LSD2 does not form a stable complex with CoREST, unlike LSD1.
- LSD2 possesses a unique CW-type zinc finger motif absent in LSD1.
Conclusions:
- Mammalian LSD2 is a novel flavin-dependent H3-Lys4 demethylase.
- LSD2 shares substrate specificity with LSD1 but operates in distinct chromatin-remodeling complexes.
- The unique structural features of LSD2 suggest specialized roles in epigenetic regulation.
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