The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation
The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation
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DOI：
10.1006/dbio.2001.0185
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发表时间：
2001-04-15
影响因子：
2.7
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
--
作者：
Kobayashi, M;Nishikawa, K;Yamamoto, M
Six3是一个在前神经板和眼原基中表达的脊椎动物同源盒基因。我们在斑马鱼胚胎中过表达Six3的显性转录激活因子或抑制因子形式，以分析其对眼睛和前脑形成的影响。将Six3的激活剂形式的RNA注射到斑马鱼胚胎中导致前神经板中rx2、pax2和emx1的表达结构域减少，导致眼和前脑发育不全。另一方面，Six 3或野生型Six 3的抑制子形式的过表达显示出与激活子形式相反的表型。我们发现Six3具有ehl相关的基序，这些基序对果蝇的转录抑制功能至关重要，在将Groucho辅阻遏物拴系到启动子中起作用。我们分离了一个斑马鱼Groucho家族基因，grg3，并证明了Six3和Grg3之间的相互作用，使用酵母双杂交分析。Six3中ehl相关基序的点突变降低了其眼睛和前脑的扩大活动及其与Grg3的相互作用。这些结果有力地证明Six3在眼睛和前脑形成中作为Groucho依赖性阻遏物发挥作用。此外，斑马鱼Six2和Six4也与Grg 3相互作用，这意味着Six家族蛋白作为转录抑制因子的保守功能。(C)北京：科学出版社.
Six3 is a vertebrate homeobox gene that is expressed in the anterior neural plate and eye anlage. We overexpressed a dominant transcriptional activator or repressor form of Six3 in zebrafish embryos to analyze their effect on eye and forebrain formation. RNA injection of the activator form of Six3 into zebrafish embryos caused reduction of the expression domains for rx2, pax2 and emx1 in the anterior neural plate, resulting in eye and forebrain hypoplasia. On the other hand, overexpression of the repressor form of Six3 or wild-type Six3 showed phenotypes opposite to those of the activator form. We found that Six3 has ehl-related motifs, motifs crucial for transcriptional repression function of Drosophila engrailed which plays a role in tethering the Groucho corepressor to the promoters. We isolated one of the zebrafsh Groucho family genes, grg3, and demonstrated an interaction between Six3 and Grg3 using yeast two-hybrid analysis. Point-mutations in the ehl-related motifs in Six3 reduced both its eye and forebrain enlarging activities and its interaction with Grg3. These results strongly argue that Six3 functions as a Groucho-dependent repressor in eye and forebrain formation. Furthermore, zebrafish Six2 and Six4 also interacted with Grg3, implying a conserved function among the Six family proteins as transcriptional repressors. (C) 2001 Academic Press.