A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins
A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins
复制标题
DOI：
10.1073/pnas.96.5.2420
复制
发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Jones, FS
中科院分区：
文献类型：
--
作者：
Meech, R;Kallunki, P;Jones, FS
细胞粘附分子L1调节发育过程中的轴突引导和成束。我们以前确定了L1基因的调控区，并表明它足以建立转基因小鼠的L1表达的神经模式。在本研究中，我们描述了该区域内的一个称为HPD的DNA元件，该元件包含同源结构域和Pax蛋白的结合基序，并响应骨形态发生蛋白（BMP）的信号。HPD核心内的ATTA序列是结合同源结构域蛋白Barx 2所必需的，而单独的配对结构域识别基序是结合Pax-6所必需的。在细胞转染实验中，含有HPD的L1-荧光素酶报告基因构建体在N2 A细胞中被Pax-6激活平均4倍，在Ng 108细胞中被BMP-2和BMP-4激活平均5倍。从L1构建体中删除HPD后，这两种反应均被消除。在转基因小鼠中，从L1-lacZ报告基因中删除HPD导致端脑和中脑中β-半乳糖苷酶表达丧失。总的来说，我们的实验表明，HPD调节L1在神经组织中的表达，通过同源结构域和Pax蛋白，并且可能是发育过程中BMP信号传导的靶点。
The cell adhesion molecule L1 regulates axonal guidance and fasciculation during development. We previously identified the regulatory region of the L1 gene and showed that it was sufficient for establishing the neural pattern of L1 expression in transgenic mice. In the present study, we characterize a DNA element within this region called the HPD that contains binding motifs for both homeodomain and Pax proteins and responds to signals from bone morphogenetic proteins (BMPs). An ATTA sequence within the core of the HPD was required for binding to the homeodomain protein Barx2 while a separate paired domain recognition motif was necessary for binding to Pax-6, In cellular transfection experiments, L1-luciferase reporter constructs containing the HPD were activated an average of 4-fold by Pax-6 in N2A cells and 5-fold by BMP-2 and BMP-4 in Ng108 cells. Both of these responses were eliminated on deletion of the HPD from L1 constructs. In transgenic mice, deletion of the HPD from an L1-lacZ reporter resulted in a loss of beta-galactosidase expression in the telencephalon and mesencephalon. Collectively, our experiments indicate that the HPD regulates L1 expression in neural tissues,ia homeodomain and Pax proteins and is likely to be a target of BMP signaling during development.