Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx NY 10461, USA.
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx NY 10461, USA; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx NY 10461, USA; Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx NY 10461, USA.
Dev Biol. 2019 May 1;449(1):41-51. doi: 10.1016/j.ydbio.2019.02.003. Epub 2019 Feb 13.
Regulation of the Drosophila ID protein Extra macrochaetae (Emc) is important because reduced Emc levels have been proposed to favor proneural gene activity and thereby define a prepattern for neurogenesis. Recent studies suggest a major role for post-translational control of Emc levels. To further define the mechanisms of Emc regulation, we identified two redundant cis-regulatory regions by germline transformation-rescue experiments that make use of new molecularly-defined emc mutants. We distinguished the mechanisms by which Daughterless (Da) regulated Emc expression, finding post-translational regulation in most tissues, and additional transcriptional regulation in the eye imaginal disc posterior to the morphogenetic furrow. Dpp and Hh signaling pathways repressed Emc transcriptionally and post-translationally within the morphogenetic furrow of the eye disc, whereas Wg signaling repressed Emc expression at the anterior margin of the wing imaginal disc. Although the emc 3' UTR is potentially regulatory, no effect of miRNA pathways on Emc protein levels was discernible. Our work supports recent evidence that post-transcriptional mechanisms contribute more to regulation of Emc protein levels than transcriptional mechanisms do.
果蝇 ID 蛋白 Extra macrochaetae(Emc)的调控非常重要,因为降低 Emc 水平被认为有利于神经前基因的活性,从而为神经发生定义一个前模式。最近的研究表明,Emc 水平的翻译后调控起着重要作用。为了进一步确定 Emc 调控的机制,我们通过生殖细胞转化拯救实验鉴定了两个冗余的顺式调控区,该实验利用了新的分子定义的 emc 突变体。我们区分了 Daughterless(Da)调节 Emc 表达的机制,发现大多数组织中存在翻译后调控,而在眼盘的胚胎发生沟后区存在额外的转录调控。Dpp 和 Hh 信号通路在眼盘的胚胎发生沟内转录和翻译后抑制 Emc 的表达,而 Wg 信号通路在翅盘的前缘抑制 Emc 的表达。尽管 emc 3'UTR 具有潜在的调节作用,但 miRNA 通路对 Emc 蛋白水平没有明显影响。我们的工作支持了最近的证据,即转录后机制对 Emc 蛋白水平的调控作用大于转录机制。