Characterization of the Regulatory Domains of the Human Skn-1a/Epoc-1/Oct-11 POU Transcription Factor*
Characterization of the Regulatory Domains of the Human Skn-1a/Epoc-1/Oct-11 POU Transcription Factor*
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人类 Skn-1a/Epoc-1/Oct-11 POU 转录因子调控域的表征*
DOI：
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发表时间：
1999
影响因子：
4.8
通讯作者：
J. Vogel
中科院分区：
文献类型：
--
作者：
Jeffrey Hildesheim;R. Foster;M. Chamberlin;J. Vogel
Skn-1a POU 转录因子主要在小鼠胚胎和成人表皮的角质形成细胞中表达。尽管一些以组织特异性方式表达的 POU 因子对于正常分化很重要，但 Skn-1a 的生物学功能仍然未知。先前的体外研究表明 Skn-1a 具有反式激活角质形成细胞分化标记物的能力。在这项研究中，我们表征了 Skn-1a 的反式激活结构域，并设计了一种缺乏该反式激活结构域的显性失活蛋白。对具有三个靶启动子的 Skn-1a 人类同源物的删除分析揭示了两个功能域的存在：一个初级 C 端反式激活域以及一个组合的 N 端抑制域和反式激活域。缺乏 C 末端区域的 Skn-1a 完全丧失了反式激活能力，无论测试的启动子如何，并且能够在竞争测定中阻断正常 Skn-1a 的反式激活。与全长相比，缺乏 N 末端区域的 Skn-1a 表现出反式激活增加（牛细胞角蛋白 6 启动子）、相当的反式激活（人乳头瘤病毒 1a 型长控制区）或反式激活丧失（人乳头瘤病毒 18 型长控制区）。主要 C 末端反式激活结构域的鉴定使我们能够生成显性失活 Skn-1a 因子，这将有助于更好地了解这种角质形成细胞特异性基因调节因子。
The Skn-1a POU transcription factor is primarily expressed in keratinocytes of murine embryonic and adult epidermis. Although some POU factors expressed in a tissue-specific manner are important for normal differentiation, the biological function of Skn-1a remains unknown. Previous in vitro studies indicate that Skn-1a has the ability to transactivate markers of keratinocyte differentiation. In this study, we have characterized Skn-1a’s transactivation domain(s) and engineered a dominant negative protein that lacked this transactivation domain. Deletional analysis of the human homologue of Skn-1a with three target promoters revealed the presence of two functional domains: a primary C-terminal transactivation domain and a combined N-terminal inhibitory domain and transactivation domain. Skn-1a lacking the C-terminal region completely lost transactivation ability, irrespective of the promoter tested, and was able to block transactivation by normal Skn-1a in competition assays. Compared with full-length, Skn-1a lacking the N-terminal region demonstrated either increased transactivation (bovine cytokeratin 6 promoter), comparable transactivation (human papillomavirus type 1a long control region), or loss of transactivation (human papillomavirus type 18 long control region). The identification of a primary C-terminal transactivation domain enabled us to generate a dominant negative Skn-1a factor, which will be useful in the quest for a better understanding of this keratinocyte-specific gene regulator.
影响因子：
4
作者：
FUCHS, E;BYRNE, C
通讯作者：
BYRNE, C
影响因子：
10.5
作者：
CLERC, RG;CORCORAN, LM;SHARP, PA
通讯作者：
SHARP, PA