Conte Ivan, Bovolenta Paola
Departamento de Neurobiología Celular, Molecular y del Desarrollo, Instituto Cajal, CSIC, Dr Arce, Madrid 28002, Spain.
Genome Biol. 2007;8(7):R137. doi: 10.1186/gb-2007-8-7-r137.
Embryonic development is coordinated by sets of cis-regulatory elements that are collectively responsible for the precise spatio-temporal organization of regulatory gene networks. There is little information on how these elements, which are often associated with highly conserved noncoding sequences, are combined to generate precise gene expression patterns in vertebrates. To address this issue, we have focused on Six3, an important regulator of vertebrate forebrain development.
Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene. Transgenesis in medaka fish demonstrates that these sequences have enhancer, silencer, and silencer blocker activities that are differentially combined to control the entire distribution of Six3.
This report provides the first example of the precise regulatory code necessary for the expression of a vertebrate gene, and offers a unique framework for defining the interplay of trans-acting factors that control the evolutionary conserved use of Six3.
胚胎发育由一组顺式调控元件协调，这些元件共同负责调控基因网络的精确时空组织。关于这些通常与高度保守的非编码序列相关的元件如何组合以在脊椎动物中产生精确的基因表达模式，目前知之甚少。为了解决这个问题，我们聚焦于Six3，它是脊椎动物前脑发育的一个重要调节因子。
通过计算分析并利用硬骨鱼基因组的多样性，我们在Six3基因周围鉴定出一组高度保守的非编码序列。在青鳉鱼中的转基因实验表明，这些序列具有增强子、沉默子和沉默子阻断活性，它们以不同方式组合以控制Six3的整体分布。
本报告提供了脊椎动物基因表达所需精确调控密码的首个实例，并为定义控制Six3进化保守使用的反式作用因子之间的相互作用提供了一个独特的框架。
