SUPPRESSOR OF HAIRLESS DIRECTLY ACTIVATES TRANSCRIPTION OF ENHANCER OF SPLIT COMPLEX GENES IN RESPONSE TO NOTCH RECEPTOR ACTIVITY
SUPPRESSOR OF HAIRLESS DIRECTLY ACTIVATES TRANSCRIPTION OF ENHANCER OF SPLIT COMPLEX GENES IN RESPONSE TO NOTCH RECEPTOR ACTIVITY
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DOI：
10.1101/gad.9.21.2609
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发表时间：
1995-11-01
影响因子：
10.5
通讯作者：
POSAKONY, JW
中科院分区：
文献类型：
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作者：
BAILEY, AM;POSAKONY, JW
我们研究了果蝇成体外周神经发生过程中，多种细胞命运选择决定所需的三个基因座之间的功能关系：Notch（N），其编码跨膜受体蛋白，无毛抑制子[Su（H）]，其编码DNA结合转录因子，和分裂基因复合物增强子[E（spl）-C]，其包括编码碱性螺旋-环-螺旋（bHLH）阻遏蛋白的七个转录单位。我们描述了几条证据，证明Su（H）直接激活E（spl）-C基因的转录，以响应N受体的活性。活化形式的N受体的表达导致升高和异位E（sp1）-C转录积累和启动子活性在成虫盘。我们发现，三个E（spl）-C基因的近端上游区域含有多个Su（H）的特异性结合位点。这些位点的完整性以及Su（H）基因活性不仅是成虫盘前神经簇中E（sp1）-C基因表达水平正常所必需的，而且也是它们对N受体过度活性的转录反应所必需的。我们的研究结果建立了Su（H）作为N受体活性和E（spl）-C基因表达之间的直接调节联系，扩展了N细胞-细胞信号传导途径的已知线性结构。
We have investigated the functional relationships among three loci that are required far multiple alternative cell fate decisions during adult peripheral neurogenesis in Drosophila: Notch (N), which encodes a transmembrane receptor protein, Suppressor of Hairless [Su(H)], which encodes a DNA-binding transcription factor, and the Enhancer of split gene complex [E(spl)-C], which includes seven transcription units that encode basic helix-loop-helix (bHLH) repressor proteins. We describe several lines of evidence establishing that Su(H) directly activates transcription of E(spl)-C genes in response to N receptor activity. Expression of an activated form of the N receptor leads to elevated and ectopic E(sp1)-C transcript accumulation and promoter activity in imaginal discs. We show that the proximal upstream regions of three E(spl)-C genes contain multiple specific binding sites for Su(H). The integrity of these sites, as well as Su(H) gene activity, are required not only for normal levels of expression of E(sp1)-C genes in imaginal disc proneural clusters, but also for their transcriptional response to hyperactivity of the N receptor. Our results establish Su(H) as a direct regulatory link between N receptor activity and the expression of E(spl)-C genes, extending the known linear structure of the N cell-cell signaling pathway.