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首页> 外文期刊>Development >Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression.
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Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression.

机译：天然构象的顺式调节模块之间的复杂相互作用对于果蝇蜗牛的表达至关重要。

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摘要

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a approximately 25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression.
机译：在几种生物中已经表明，基因座的多个顺式调控模块（CRM）可以同时激活以支持相似的时空表达。为了了解这种看似多余的CRM的功能重要性，我们检查了果蝇蜗牛基因位点的两种CRM，它们均在妊娠前胚胎的腹侧区域活跃。通过使用BAC重组和定点转基因在大约25 kb DNA营救构建体中执行缺失序列，我们证明了这两个CRM并不是多余的。为了生存，绝对需要远端CRM，而只有在高温等极端条件下才需要远端CRM。根据其不同的要求，CRM支持不同的表达模式：相对于内源性蜗牛，近端CRM展现出扩展的表达域，而除了最前极，远端CRM几乎与蜗牛重叠。我们进一步表明，远端CRM通常会限制近端CRM的表达区域增加，而近端CRM则是远端CRM驱动的表达水平的“抑制器”。因此，两个CRM以非加性方式顺式相互作用，并且这些相互作用对于微调基因表达的域和水平可能很重要。

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