INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila.

INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila.
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依赖于ecdysone诱导的转录反应的INO80依赖性回归调节果蝇的发育时机。

DOI:
10.1016/j.ydbio.2014.01.006
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发表时间:
2014-03-15
影响因子:
2.7
通讯作者:
Bashirullah, Arash
Bashirullah, Arash
中科院分区:
生物学3区
文献类型:
--
作者:
Neuman, Sarah D.;Ihry, Robert J.;Gruetzmacher, Kelly M.;Bashirullah, Arash

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类固醇激素蜕皮激素的连续脉冲调节果蝇的主要发育转变,并且每个发育阶段的持续时间由蜕皮激素脉冲之间的时间长度决定。蜕皮激素通过直接启动靶基因转录来调节生物反应。反过来,已知这些转录反应是自限性的,其机制确保了依赖于转录的逆转。然而,这些转录抑制机制的生物学意义仍不清楚。在这里,我们表明,染色质重塑蛋白ino 80促进蜕皮激素调控基因的转录抑制在预蛹的发展。在ino 80突变体动物中,对晚期幼虫蜕皮激素脉冲的转录反应的低效抑制延迟了随后的预蛹蜕皮激素脉冲的发作,从而导致显著更长的预蛹阶段。相反,增加ino 80的表达足以通过增加转录抑制的速率来缩短预蛹阶段。此外,我们还证明,提高预蛹中期能力因子βFTZ-F1的回归率足以确定头外翻的时间,从而确定预蛹发育的持续时间。虽然ino 80从酵母到人类是保守的,但这项研究首次表征了任何后生动物中真正的ino 80突变,提高了ino 80在转录抑制和发育时序中的功能在进化上保守的可能性。
Sequential pulses of the steroid hormone ecdysone regulate the major developmental transitions in Drosophila, and the duration of each developmental stage is determined by the length of time between ecdysone pulses. Ecdysone regulates biological responses by directly initiating target gene transcription. In turn, these transcriptional responses are known to be self-limiting, with mechanisms in place to ensure regression of hormone-dependent transcription. However, the biological significance of these transcriptional repression mechanisms remains unclear. Here we show that the chromatin remodeling protein ino80 facilitates transcriptional repression of ecdysone-regulated genes during prepupal development. In ino80 mutant animals, inefficient repression of transcriptional responses to the late larval ecdysone pulse delays the onset of the subsequent prepupal ecdysone pulse, resulting in a significantly longer prepupal stage. Conversely, increased expression of ino80 is sufficient to shorten the prepupal stage by increasing the rate of transcriptional repression. Furthermore, we demonstrate that enhancing the rate of regression of the mid-prepupal competence factor βFTZ-F1 is sufficient to determine the timing of head eversion and thus the duration of prepupal development. Although ino80 is conserved from yeast to humans, this study represents the first characterization of a bona fide ino80 mutation in any metazoan, raising the possibility that the functions of ino80 in transcriptional repression and developmental timing are evolutionary conserved.
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