A global control region defines a chromosomal regulatory landscape containing the HoxD cluster
A global control region defines a chromosomal regulatory landscape containing the HoxD cluster
复制标题
DOI：
10.1016/s0092-8674(03)00310-6
复制
发表时间：
2003-05-02
期刊：
影响因子：
64.5
通讯作者：
Duboule, D
中科院分区：
文献类型：
--
作者：
Spitz, F;Gonzalez, F;Duboule, D
在肢体发育过程中，几个Hoxd基因的协调表达需要在推定的数字。我们搜索了簇上游的潜在控制序列，发现了Lunapark（Lnp），一个与Hoxd基因和Evx 2（位于附近的另一个基因）共享肢体和CNS表达特异性的基因。我们使用了一个有针对性的增强子陷阱的方法，以确定一个DNA片段能够指导报告基因表达的数字和中枢神经系统，以下LNP，Evx2，和Hoxd的具体模式。这个DNA区域显示出一种不寻常的物种间保护，包括与河豚的对应物。它包含一簇全局增强子，能够控制结构或功能无关的几个基因的转录，从而定义了大的调控域。这些结构域在无尺骨突变中被中断，这是一种平衡倒位，改变了基因座的地形。我们讨论的启发式价值，这些结果在基因座特异性与基因特异性调节。
During limb development, coordinated expression of several Hoxd genes is required in presumptive digits. We searched for the underlying control sequences upstream from the cluster and found Lunapark (Lnp), a gene which shares limb and CNS expression specificities with both Hoxd genes and Evx2, another gene located nearby. We used a targeted enhancer-trap approach to identify a DNA segment capable of directing reporter gene expression in both digits and CNS, following Lnp, Evx2, and Hoxd-specific patterns. This DNA region showed an unusual interspecies conservation, including with its pufferfish counterpart. It contains a cluster of global enhancers capable of controlling transcription of several genes unrelated in structure or function, thus defining large regulatory domains. These domains were interrupted in the Ulna-less mutation, a balanced inversion that modified the topography of the locus. We discuss the heuristic value of these results in term of locus specific versus gene-specific regulation.