Kazutaka Akagi

Publications (3)12.27 Total impact

• Source

  Available from: Susumu Hirose

  Article: 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, Yasushi Kayashima, Yusuke Takakura, Susumu Hirose, Hitoshi Ueda
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  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. 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.
  Journal of Molecular Biology 11/2012; · 4.00 Impact Factor
• Article: Regulatory mechanisms of ecdysone-inducible Blimp-1 encoding a transcriptional repressor that is important for the prepupal development in Drosophila.

  Kazutaka Akagi, Hitoshi Ueda
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  ABSTRACT: Blimp-1 is an ecdysone-inducible transcription factor that is expressed in the early stage of the prepupal period. The timing of its disappearance determines expression timing of the FTZ-F1 gene, whose temporally restricted expression is essential for the prepupal development. To elucidate the termination mechanism of Blimp-1 gene expression, we examined the regulation of the Blimp-1 gene using an organ culture system. The results showed that the Blimp-1 gene is transcribed in cultured organs taken from a low ecdysteroid period even after extended exposure to 20-hydroxyecdysone, while well-known early genes such as E75A are repressed under the same conditions. Similar selective transcription was observed in the cultured organs obtained from a high ecdysteroid period. We further showed that Blimp-1 transcripts quickly disappeared in the presence of actinomycin D. From these results, we concluded that the Blimp-1 gene is transcribed when the ecdysteroid titer is high, but the expressed mRNA degrades rapidly; these unique regulations limit its expression to the high ecdysteroid stage.
  Embryologia 06/2011; 53(5):697-703. · 2.21 Impact Factor
• Source

  Available from: Susumu Hirose

  Article: Drosophila Blimp-1 is a transient transcriptional repressor that controls timing of the ecdysone-induced developmental pathway.

  Yasuo Agawa, Moustafa Sarhan, Yuji Kageyama, Kazutaka Akagi, Masayoshi Takai, Kazuya Hashiyama, Tadashi Wada, Hiroshi Handa, Akihiro Iwamatsu, Susumu Hirose, Hitoshi Ueda
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  ABSTRACT: Regulatory mechanisms controlling the timing of developmental events are crucial for proper development to occur. ftz-f1 is expressed in a temporally regulated manner following pulses of ecdysteroid and this precise expression is necessary for the development of Drosophila melanogaster. To understand how insect hormone ecdysteroids regulate the timing of FTZ-F1 expression, we purified a DNA binding regulator of ftz-f1. Mass spectroscopy analysis revealed this protein to be a fly homolog of mammalian B lymphocyte-induced maturation protein 1 (Blimp-1). Drosophila Blimp-1 (dBlimp-1) is induced directly by 20-hydroxyecdysone, and its product exists during high-ecdysteroid periods and turns over rapidly. Forced expression of dBlimp-1 and RNA interference analysis indicate that dBlimp-1 acts as a repressor and controls the timing of FTZ-F1 expression. Furthermore, its prolonged expression results in delay of pupation timing. These results suggest that the transient transcriptional repressor dBlimp-1 is important for determining developmental timing in the ecdysone-induced pathway.
  Molecular and cellular biology 01/2008; 27(24):8739-47. · 6.06 Impact Factor