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首页> 外文期刊>Development >E-cadherin intron 2 contains cis-regulatory elements essential for gene expression.
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E-cadherin intron 2 contains cis-regulatory elements essential for gene expression.

机译：E-cadherin内含子2包含基因表达必不可少的顺式调控元件。

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Cadherin-mediated cell-cell adhesion plays important roles in mouse embryonic development, and changes in cadherin expression are often linked to morphogenetic events. For proper embryonic development and organ formation, the expression of E-cadherin must be tightly regulated. Dysregulated expression during tumorigenesis confers invasiveness and metastasis. Except for the E-box motifs in the E-cadherin promoter, little is known about the existence and location of cis-regulatory elements controlling E-cadherin gene expression. We have examined putative cis-regulatory elements in the E-cadherin gene and we show a pivotal role for intron 2 in activating transcription. Upon deleting the genomic intron 2 entirely, the E-cadherin locus becomes completely inactive in embryonic stem cells and during early embryonic development. Later in development, from E11.5 onwards, the locus is activated only weakly in the absence of intron 2 sequences. We demonstrate that in differentiated epithelia, intron 2 sequences are required both to initiate transcriptional activation and additionally to maintain E-cadherin expression. Detailed analysis also revealed that expression in the yolk sac is intron 2 independent, whereas expression in the lens and the salivary glands absolutely relies on cis-regulatory sequences of intron 2. Taken together, our findings reveal a complex mechanism of gene regulation, with a vital role for the large intron 2.
机译：钙黏着蛋白介导的细胞间黏附在小鼠胚胎发育中起重要作用，并且钙黏着蛋白表达的变化通常与形态发生事件有关。为了适当的胚胎发育和器官形成，必须严格调节E-cadherin的表达。肿瘤发生过程中表达失调会导致浸润和转移。除了E-钙粘蛋白启动子中的E-box基序外，对控制E-钙粘蛋白基因表达的顺式调节元件的存在和位置知之甚少。我们已经检查了E-钙粘着蛋白基因中的假定的顺式调控元件，并且我们显示了内含子2在激活转录中的关键作用。完全删除基因组内含子2后，E-钙粘着蛋白基因座在胚胎干细胞和早期胚胎发育过程中变得完全无活性。从E11.5开始的后期开发中，基因座仅在缺乏内含子2序列的情况下才被弱激活。我们证明，在分化的上皮细胞中，内含子2序列既需要启动转录激活，又需要维持E-钙粘蛋白的表达。详细分析还显示，卵黄囊中的表达是独立于内含子2的，而晶状体和唾液腺中的表达绝对依赖于内含子2的顺式调控序列。总的来说，我们的发现揭示了复杂的基因调控机制，其中内含子的重要作用2。

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