Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity
Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity
复制标题
DOI：
10.1006/dbio.1998.9128
复制
发表时间：
1999-01-01
影响因子：
2.7
通讯作者：
Gruss, P
中科院分区：
文献类型：
--
作者：
Kammandel, B;Chowdhury, K;Gruss, P
Pax 6是一种调控基因，在发育中的眼和胰腺以及CNS的不同结构域中具有限制性表达和基本功能。在这项研究中，我们报告的三个保守的转录起始位点（P0，P1，α）在小鼠Pax 6基因座的鉴定。此外，使用转基因小鼠技术，我们本地化独立的顺式调控元件控制Pax 6的组织特异性表达。具体地说，需要一个107-bp的增强子和外显子0上游4.6-kb非翻译区内的1.1-kb序列分别介导Pax 6在透镜、角膜、泪腺、结膜或胰腺中的表达。位于Pax 6翻译起始位点下游的另一个530 bp增强子片段是在神经视网膜、视网膜色素层和虹膜中表达所需的。最后，位于启动子P0和P1之间的5-kb片段可以介导端脑背侧、后脑和脊髓中的表达。所确定的Pax 6/顺式必需元件在河豚鱼、小鼠和人的DNA中高度保守，并且含有指示级联控制事件的几个转录因子的结合位点。来自河豚鱼的相应调控元件能够模拟转基因小鼠中的报告基因表达。因此，结果表明脊椎动物基因组中Pax 6调控元件的结构和功能保守。(C)北京：科学出版社.
Pax6 is a regulatory gene with restricted expression and essential functions in the developing eye and pancreas and distinct domains of the CNS. In this study we report the identification of three conserved transcription start sites (P0, P1, alpha) in the murine Pax6 locus. Furthermore, using transgenic mouse technology we localized independent cis-regulatory elements controlling the tissue-specific expression of Pax6. Specifically, a 107-bp enhancer and a 1.1-kb sequence within the 4.6-kb untranslated region upstream of exon 0 are required to mediate Pax6 expression in the lens, cornea, lacrimal gland, conjunctiva, or pancreas, respectively. Another 530-bp enhancer fragment located downstream of the Pax6 translational start site is required for expression in the neural retina, the pigment layer of the retina, and the iris. Finally, a 5-kb fragment located between the promoters P0 and P1 can mediate expression into the dorsal telencephalon, the hindbrain, and the spinal cord. The identified Pax6/cis-essential elements are highly conserved in pufferfish, mouse, and human DNA and contain binding sites for several transcription factors indicative of the cascade of control events. Corresponding regulatory elements from pufferfish are able to mimic the reporter expression in transgenic mice. Thus, the results indicate a structural and functional conservation of the Pax6 regulatory elements in the vertebrate genome. (C) 1999 Academic Press.