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首页> 外文期刊>PLoS Genetics >Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements
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Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements

机译：Kroox20后脑调节包括联合人工具元素之间多种合作模式

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摘要

Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.
机译：发育基因可以含有多种转录增强剂，其同时或连续地实现稳健和精确的时空表达。然而，CIS作用元素之间的合作机制符合脊椎动物的良好记录。小鼠基因Krox20编码了显影后脑的两段（菱形）的规范所需的转录因子。在菱形3中，KrOx20受到自动调节增强剂，元素A的直接阳性反馈。相反，从转录的转录的开始，第二增强剂，远处的升高的Engancer，Elemant C，与KrOx20蛋白的存在无关。 。在这里，使用增强剂爆震和染色质组织的研究，我们表明元素C具有双重活动：除了其经典的增强功能外，CI中也是永久性的，以通过增加其染色质来提高元素A的自身调节活性。可访问性。这项工作揭示了独联体作用元件之间的新颖，不对称，远程合作模式，这可能是必不可少的，以避免阳性自动调节元素的混杂性激活。

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