The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
复制标题
DOI：
10.1242/bio.2011047
复制
发表时间：
2012-03-15
期刊：
影响因子：
2.4
通讯作者：
Tsai, Chih-Cheng
中科院分区：
文献类型：
--
作者：
Heck, Bryan W.;Zhang, Bin;Tsai, Chih-Cheng
SMRTER(SMRT相关和蜕皮激素受体相互作用因子)是脊椎动物蛋白SMRT和N-COR的果蝇同源物，与它们形成一个高度保守的转录辅阻遏子家族。培养细胞中SMRT家族蛋白的分子特征表明它们参与了广泛的转录调控途径。然而，目前对这类保守的转录辅阻遏子如何通过特定的途径调节特定组织的发育知之甚少。在这项研究中，通过我们对多个SMR突变系的鉴定，一个功能缺失的SMR等位基因的镶嵌分析，以及对两个独立的SMR RNAi苍蝇系的研究，我们报告了SMRTER对卵巢卵泡细胞和翅膀的发育都是必需的。在这两个组织中，SMRTER不仅抑制蜕皮激素途径，还抑制Notch途径。我们通过表明SMRTER以时空受限的方式抑制Notch途径而不是蜕皮激素途径来区分SMRTER对这两个信号通路的影响。我们通过证明SMRTER与Notch途径中的DNA结合转录因子SU(H)的抑制子SU(H)之间的直接相互作用，以及两种蛋白在唾液腺中的多个染色体区域的共存，进一步证实了SMRTER可能参与了Notch途径。根据我们的结果，我们认为SMRTER通过与SU(H)的联系来调节Notch途径，克服SMRTER介导的转录抑制障碍可能是Notch途径在发育过程中控制事件的精确时间和细胞之间尖锐边界形成的关键机制。(C)2011年。生物学家有限公司出版。
SMRTER (SMRT-related and ecdysone receptor interacting factor) is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicated them in a wide range of transcriptional regulatory pathways. However, little is currently known about how this conserved class of transcriptional corepressors regulates the development of particular tissues via specific pathways. In this study, through our characterization of multiple Smrter (Smr) mutant lines, mosaic analysis of a loss-of-function Smr allele, and studies of two independent Smr RNAi fly lines, we report that SMRTER is required for the development of both ovarian follicle cells and the wing. In these two tissues, SMRTER inhibits not only the ecdysone pathway, but also the Notch pathway. We differentiate SMRTER's influence on these two signaling pathways by showing that SMRTER inhibits the Notch pathway, but not the ecdysone pathway, in a spatiotemporally restricted manner. We further confirm the likely involvement of SMRTER in the Notch pathway by demonstrating a direct interaction between SMRTER and Suppressor of Hairless [ Su(H)], a DNA-binding transcription factor pivotal in the Notch pathway, and the colocalization of both proteins at many chromosomal regions in salivary glands. Based on our results, we propose that SMRTER regulates the Notch pathway through its association with Su(H), and that overcoming a SMRTER-mediated transcriptional repression barrier may represent a key mechanism used by the Notch pathway to control the precise timing of events and the formation of sharp boundaries between cells in multiple tissues during development. (C) 2011. Published by The Company of Biologists Ltd.