Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the Delta-Notch signal transduction pathway in Drosophila
Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the Delta-Notch signal transduction pathway in Drosophila
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DOI：
10.1534/genetics.105.041327
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发表时间：
2005-08-01
期刊：
影响因子：
3.3
通讯作者：
Tamkun, JW
中科院分区：
文献类型：
--
作者：
Armstrong, JA;Sperling, AS;Tamkun, JW
果蝇三胸组基因 brahma (brm) 编码 2-MDa 染色质重塑复合物的 ATP 酶亚基。 brat 在同源基因转录激活子筛选中被鉴定出来，随后显示其在 RNA 聚合酶 II 的转录中发挥着全局作用。为了深入了解 BRM 复合物的靶向、功能和调节，我们筛选了与 brm 显性失活等位基因 (brm(K804R)) 发生遗传相互作用的突变。我们首先筛选了与 brut 启动子控制下的 brmK804R 转基因结合致命的显性突变。在一项独特但相关的筛选中，我们发现了显性突变，这些突变可以改变因眼触角成虫盘中 brm K-804R 表达而导致的眼部缺陷。我们的筛选中发现了三类基因的突变：编码 BRM 复合体亚基的基因（brm、moira 和 osa）、直接参与转录的其他蛋白质（zerknullt 和 RpII140）以及信号分子（Delta 和 Veve）。成体感觉器官前体谱系中 brmK804R 的表达导致与 Delta-Notch 信号传导受损所产生的表型相似的表型。我们的结果表明信号通路可能通过调节 BRM 复合物的活性来调节靶基因的转录。
The Drosophila trithorax group gene brahma (brm) encodes the ATPase subunit of a 2-MDa chromatin-remodeling complex. brat was identified in a screen for transcriptional activators of homeotic genes and subsequently shown to play a global role in transcription by RNA polymerase II. To gain insight into the targeting, function, and regulation of the BRM complex, we screened for mutations that genetically interact with a dominant-negative allele of brm (brm(K804R)). We first screened for dominant mutations that are lethal in combination with a brmK804R transgene under control of the brut promoter. In a distinct but related screen, we identified dominant mutations that modify eye defects resulting from expression of brm K-804R in the eye-antennal imaginal disc. Mutations in three classes of genes were identified in our screens: genes encoding subunits of the BRM complex (brm, moira, and osa), other proteins directly involved in transcription (zerknullt and RpII140), and signaling molecules (Delta and vein). Expression of brmK804R in the adult sense organ precursor lineage causes phenotypes similar to those resulting from impaired Delta-Notch signaling. Our results suggest that signaling pathways may regulate the transcription of target genes by regulating the activity of the BRM complex.