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Published on: December 19, 2011
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Epigenetic regulation affects gene amplification in Drosophila development
Hidetsugu Kohzaki1, Maki Asano, Yota Murakami2
1Faculty of Teacher Education, Shumei University, Daigakucho 1-1, Yachiyo, Chiba, Japan 276-0003, kohzaki@mailg.shume-u.ac.jp.
Frontiers in Bioscience (Landmark Edition)
|October 6, 2019
Summary
Ecdysone signaling in Drosophila melanogaster controls DNA replication origins for chorion gene amplification. This process involves histone modifications and offers targets for epigenetic drug development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- DNA replication origins form onion skin-like structures in Drosophila ovarian follicle cells during chorion gene amplification.
- Origin recognition complex (ORC) subunits (Orc1, Orc2, Cdc6) are crucial for DNA replication, with mutations impacting viability and overexpression causing sterility.
Purpose of the Study:
- To investigate the role of ecdysone signaling in regulating DNA replication initiation at gene amplification loci.
- To explore the connection between histone modifications, ecdysone signaling, and female fertility in Drosophila.
Main Methods:
- Identification of ecdysone receptor (EcR) binding sites near gene amplification loci.
- Analysis of histone modifications, specifically H3K4 trimethylation, at chorion gene origins and control loci.
- Phenotypic analysis of female mutants overexpressing histone demethylases (Lsd1, Lid).
Main Results:
- Ecdysone receptor binding sites were found around gene amplification loci.
- H3K4 trimethylation was enriched at chorion gene amplification origins.
- Overexpression of Lsd1 or Lid led to female sterility, suggesting a role for histone demethylation in fertility.
Conclusions:
- Ecdysone signaling dictates which replication origins initiate DNA replication, contributing to developmental processes.
- Drosophila serves as a model for developing drugs targeting gene amplification and epigenetic modifications.
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