Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (4C-seq)

Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Circular Chromosome Conformation Capture (4C-seq) samples from mouse digit cells and mouse genital tubercle cells performed as previously described (Noordermeer et al. 2011)同源框基因（Hox genes）在脊椎动物指（趾）与外生殖器的形态发生过程中均发挥必需作用。本研究探究了在这两种截然不同的发育场景中，基因转录是否共享一套包含增强子的调控景观。研究显示二者采用了相同的调控拓扑结构，但同时存在部分组织特异性的增强子-启动子互作，这提示调控骨架可从一种发育场景跨域借用于另一场景。此外，在经由祖先无脊椎动物基因组复制事件分化而来的HoxA与HoxD基因簇中，均观察到了类似的调控组织形式。本研究提出，这种趋同性调控演化是由预先存在的染色质架构所触发的，进而助力后续适配性转录因子的招募。这类调控拓扑结构既可能推动脊椎动物多效性发育位点的演化，同时也对其施加了约束。本研究采用的小鼠指（趾）细胞与小鼠生殖器结节细胞的环状染色体构象捕获（Circular Chromosome Conformation Capture, 4C-seq）样本，均按照此前报道的方法制备（Noordermeer等人，2011）