Zeste tunes the timing of ecdysone actions in triggering programmed tissue degeneration in Drosophila.
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In the pupal stage, the fly body undergoes extensive metamorphic remodeling, in which programmed cell death plays a critical role. We studied two of the constituent processes in this remodeling, salivary gland degeneration and breakdown of the eclosion muscle, which are triggered by an increase and a decrease in the circulating steroid hormone ecdysone at the start and end of metamorphosis, respectively. We found that knockdown of zeste (z), a gene encoding a sequence-specific DNA-binding protein implicated in transvection, in salivary gland cells advances the initiation of their degeneration, whereas z knockdown in neurons delays muscle breakdown. We further showed that knockdown of an ecdysone-inducible gene, E74, retards salivary gland degeneration with little effect on eclosion muscle breakdown. We propose that Z tunes the sensitivity of ecdysone targets to this hormone in order to ensure a high safety margin so that the cell death program will be activated when the ecdysone titer is at a sufficiently high level that is reached only at a defined stage during metamorphosis.