IMR Press / FBL / Volume 25 / Issue 4 / DOI: 10.2741/4825

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Epigenetic regulation affects gene amplification in Drosophila development
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1 Faculty of Teacher Education, Shumei University, Daigakucho 1-1, Yachiyo, Chiba, Japan 276-0003
2 Department of Molecular Cellular and Biochemistry, The Ohio State Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
3 Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo, Hokkaido, Japan 060-0810
4 Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Send correspondence to: Hidetsugu Kohzaki, Faculty of Teacher Education, Shumei University, Daigakucho 1-1, Yachiyo, Chiba, Japan 276-0003, Tel: 81-47-409-1479, Fax: 81-47-409-9357, E-mail:
Front. Biosci. (Landmark Ed) 2020, 25(4), 632–645;
Published: 1 January 2020

In Drosophila melanogaster, in response to developmental transcription factors, and by repeated initiation of DNA replication of four chorion genes, ovarian follicle cells, form an onion skin-type structure at the replication origins. The DNA replication machinery is conserved from yeast to humans. Subunits of the origin recognition complex (ORC) is comprised of Orc1, Orc2, and Cdc6 genes. While mutations of Orc1 and Orc2 and not Cdc6can be lethal, overexpression of these genes lead to female sterility. Ecdysone, is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone that in Drosophila, triggers molting, metamorphosis, and oogenesis. To this end, we identified several ecdysone receptor (EcR) binding sites around gene amplification loci. We also found that H3K4 was trimethylated at chorion gene amplification origins, but not at the act1 locus. Female mutants overexpressing Lsd1 (a dimethyl histone H3K4 demethylase) or Lid (a trimethyl histone H3K4 demethylase), but not a Lid mutant, were sterile. The data suggest that ecdysone signaling determines which origin initiates DNA replication and contributes to the development. Screening strategies using Drosophila offer the opportunity for development of drugs that reduce gene amplification and alter histone modification associated with epigenetic effects.

gene amplification
Figure 1
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