Identification of an Upstream Enhancer in the Mouse Lamininα1 Gene Defining Its High Level of Expression in Parietal Endoderm Cells*
Identification of an Upstream Enhancer in the Mouse Lamininα1 Gene Defining Its High Level of Expression in Parietal Endoderm Cells*
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小鼠层粘连蛋白α1基因上游增强子的鉴定，决定了其在壁内胚层细胞中的高水平表达*
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
K. Sekiguchi
中科院分区：
文献类型：
--
作者：
T. Niimi;Y. Hayashi;K. Sekiguchi
层粘连蛋白-1是胚胎基底膜的主要成分，由α1、β1和γ1链组成。层粘连蛋白-1的表达诱导小鼠F9胚胎癌细胞分化成壁内胚层后，通过转录上调基因编码这些亚基。在此，我们在小鼠层粘连蛋白α1（LAMA 1）基因的5′-侧翼区鉴定了一个435-bp的增强子，该增强子以分化依赖的方式激活其转录。该增强子在PYS-2壁层卵黄囊来源的细胞中也有活性，但在NIH/3 T3成纤维细胞中没有活性，表明它是壁层内胚层特异性增强子。这种增强子在Engelbreth-Holm-Swarm（EHS）肿瘤衍生的细胞中也有活性，其特征在于过度产生层粘连蛋白-1和其他基底膜成分，这表明EHS肿瘤具有与壁内胚层细胞相似的转录控制机制。电泳迁移率变动分析显示，在435 bp的区域中有四个蛋白结合位点（PBS 1-PBS 4）。然而，这些DNA结合蛋白不仅在壁内胚层细胞（即分化的F9细胞、PYS-2细胞和EHS肿瘤来源的细胞）中检测到，而且在未分化的F9细胞和NIH/3 T3细胞中也检测到。突变分析表明，这些结合位点（PBS 2，PBS 3，和PBS 4）的功能协同赋予壁内胚层特异性增强子活性。与PBS 2和PBS 4结合的蛋白分别被鉴定为转录因子Sp1/Sp3家族和YY 1。
Laminin-1 is the major component of the embryonic basement membrane and consists of α1, β1, and γ1 chains. The expression of laminin-1 is induced in mouse F9 embryonal carcinoma cells upon differentiation into parietal endoderm through transcriptional up-regulation of the genes encoding these subunits. Here, we identified a 435-bp enhancer in the 5′-flanking region of the mouse laminin α1 (LAMA1) gene that activated its transcription in a differentiation-dependent manner. This enhancer was also active in PYS-2 parietal yolk sac-derived cells but not in NIH/3T3 fibroblasts, indicating that it was a parietal endoderm-specific enhancer. This enhancer was also active in Engelbreth-Holm-Swarm (EHS) tumor-derived cells characterized by excessive production of laminin-1 and other basement membrane components, suggesting that EHS tumors have a transcriptional control mechanism similar to that of parietal endoderm cells. Electrophoretic mobility shift analyses revealed four protein binding sites (PBS1-PBS4) in the 435-bp region. However, these DNA-binding proteins were detected not only in parietal endoderm cells (i.e. differentiated F9 cells, PYS-2 cells, and EHS tumor-derived cells) but also in undifferentiated F9 cells and NIH/3T3 cells. Mutational analyses revealed that three of these binding sites (PBS2, PBS3, and PBS4) function synergistically to confer the parietal endoderm-specific enhancer activity. The proteins binding to PBS2 and PBS4 were identified as the Sp1/Sp3 family of transcription factors and YY1, respectively.
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DOI：
10.1002/tera.1420410403
发表时间：
1990-04-01
期刊：
TERATOLOGY
影响因子：
--
作者：
JOLLIE, WP
通讯作者：
JOLLIE, WP
影响因子：
14.9
作者：
Higaki, Y;Schullery, D;Bomsztyk, K
通讯作者：
Bomsztyk, K
DOI：
10.1002/j.1460-2075.1991.tb08055.x
发表时间：
1991-05
期刊：
The EMBO Journal
影响因子：
--
作者：
G. Vasios;S. Mader;J. D. Gold;M. Leid;Y. Lutz;M. Gaub;P. Chambon;L. Gudas
通讯作者：
G. Vasios;S. Mader;J. D. Gold;M. Leid;Y. Lutz;M. Gaub;P. Chambon;L. Gudas
DOI：
10.1073/pnas.90.13.6145
发表时间：
1993-07-01
影响因子：
11.1
作者：
LEE, JS;GALVIN, KM;SHI, Y
通讯作者：
SHI, Y
DOI：
10.1073/pnas.86.23.9099
发表时间：
1989-12
影响因子：
11.1
作者：
George W. Vasios;Joseph D. Gold;M. Petkovich;P. Chambon;L. Gudas
通讯作者：
George W. Vasios;Joseph D. Gold;M. Petkovich;P. Chambon;L. Gudas