TRANSCRIPTIONAL REPRESSION BY DROSOPHILA AND MAMMALIAN POLYCOMB GROUP PROTEINS IN TRANSFECTED MAMMALIAN-CELLS

TRANSCRIPTIONAL REPRESSION BY DROSOPHILA AND MAMMALIAN POLYCOMB GROUP PROTEINS IN TRANSFECTED MAMMALIAN-CELLS
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DOI:
10.1128/mcb.14.3.1721
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发表时间:
1994-03-01
影响因子:
5.3
通讯作者:
KINGSTON, RE
KINGSTON, RE
中科院分区:
生物学2区
文献类型:
--
作者:
BUNKER, CA;KINGSTON, RE

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Polycomb组(Pc-G)基因是维持果蝇发育过程中同源异型基因座的空间限制性表达模式所必需的。Pc-G蛋白似乎在靶基因座发挥功能以维持转录抑制状态。小鼠癌基因bmi-1与Pc-G基因后性梳(Psc)和高度相关的基因Zeste的抑制子2具有显著的同源性[Sn(z)2]。我们在此表明,在共转染系统中,当通过莱克萨靶向启动子时,由bmi-1和Pc-G基因Polycomb(Pc)和Psc以及Su(z)2编码的蛋白质介导哺乳动物细胞中的阻遏。这些融合蛋白抑制激活功能多达30倍,不同的激活结构域的影响是不同的每一个Pc-G蛋白。当莱克萨融合蛋白与激活剂结合位点直接相邻结合时,以及当与启动子1,700个碱基结合时,观察到抑制。这些数据表明,Pc-G基因的产物可以显著抑制瞬时引入的DNA上的激活子功能。我们认为,这一功能有助于在发展过程中的目标位点的稳定镇压。
The Polycomb group (Pc-G) genes are essential for maintaining the proper spatially restricted expression pattern of the homeotic loci during Drosophila development. The Pc-G proteins appear to function at target loci to maintain a state of transcriptional repression. The murine oncogene bmi-1 has significant homology to the Pc-G gene Posterior sex combs (Psc) and a highly related gene, Suppressor two of zeste [Sn(z)2]. We show here that the proteins encoded by bmi-l and the Pc-G genes Polycomb (Pc) and Psc as well as Su(z)2 mediate repression in mammalian cells when targeted to a promoter by LexA in a cotransfection system. These fusion proteins repress activator function by as much as 30-fold, and the effect on different activation domains is distinct for each Pc-G protein. Repression is observed when the LexA fusion proteins are bound directly adjacent to activator binding sites and also when bound 1,700 bases from the promoter. These data demonstrate that the products of the Pc-G genes can significantly repress activator function on transiently introduced DNA. We suggest that this function contributes to the stable repression of targeted loci during development.