The Binding of Multiple Nuclear Receptors to a Single Regulatory Region Is Important for the Proper Expression of EDG84A in Drosophila melanogaster

Kazutaka Akagi, Yuji Kageyama, Yasunari Kayashima, Yusuke Takakura, Susumu Hirose, Hitoshi Ueda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Nuclear receptor transcription factor family members share target sequence similarity; however, little is known about how these factors exert their specific regulatory control. Here, we examine the mechanism regulating the expression of the Drosophila EDG84A gene, a target gene of the orphan nuclear receptor βFTZ-F1, as a model to study the cooperative behavior among nuclear receptors. We show that the three nuclear receptors βFTZ-F1, DHR3, and DHR39 bind to a common element in the EDG84A promoter. The expression level of the EDG84A promoter-lacZ reporter genes in DHR39-induced and mutant animals, respectively, suggests that DHR39 works as a repressor. The activity of a reporter gene carrying a mutation preventing DHR3 binding was reduced in ftz-f1 mutants and rescued by the induced expression of βFTZ-F1, suggesting that DHR3 and βFTZ-F1 activate the EDG84A gene in a redundant manner. A reporter gene carrying a mutation that abolishes DHR39 and FTZ-F1 binding was prematurely expressed, and the expression level of the reporter gene carrying a mutation preventing DHR3 binding was reduced. These findings suggest that the temporal expression of this gene is mainly controlled by βFTZ-F1 but that the binding of DHR3 is also important. Comparison of the binding site sequence among Drosophila species suggests that DHR3 binding ability was gained after the melanogaster subgroup evolved, and this ability may contribute to the robust expression of this gene. These results show the complicated regulatory mechanisms utilized by multiple nuclear receptors to properly regulate the expression of their target gene through a single target site.

Original languageEnglish
Pages (from-to)71-81
Number of pages11
JournalJournal of Molecular Biology
Volume425
Issue number1
DOIs
Publication statusPublished - Jan 9 2013

Fingerprint

Nucleic Acid Regulatory Sequences
Cytoplasmic and Nuclear Receptors
Drosophila melanogaster
Reporter Genes
Aptitude
Mutation
Genes
Drosophila
Orphan Nuclear Receptors
Gene Expression
Lac Operon
Cooperative Behavior
Transcription Factors
Binding Sites

Keywords

  • DHR3
  • Drosophila
  • FTZ-F1
  • gene regulation
  • nuclear receptor

ASJC Scopus subject areas

  • Molecular Biology

Cite this

The Binding of Multiple Nuclear Receptors to a Single Regulatory Region Is Important for the Proper Expression of EDG84A in Drosophila melanogaster. / Akagi, Kazutaka; Kageyama, Yuji; Kayashima, Yasunari; Takakura, Yusuke; Hirose, Susumu; Ueda, Hitoshi.

In: Journal of Molecular Biology, Vol. 425, No. 1, 09.01.2013, p. 71-81.

Research output: Contribution to journalArticle

Akagi, Kazutaka ; Kageyama, Yuji ; Kayashima, Yasunari ; Takakura, Yusuke ; Hirose, Susumu ; Ueda, Hitoshi. / The Binding of Multiple Nuclear Receptors to a Single Regulatory Region Is Important for the Proper Expression of EDG84A in Drosophila melanogaster. In: Journal of Molecular Biology. 2013 ; Vol. 425, No. 1. pp. 71-81.
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