Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, Carretera de Utrera Km1, 41013 Sevilla, Spain.
Nat Commun. 2011;2:310. doi: 10.1038/ncomms1301.
Developmental gene clusters are paradigms for the study of gene regulation; however, the mechanisms that mediate phenomena such as coregulation and enhancer sharing remain largely elusive. Here we address this issue by analysing the vertebrate Irx clusters. We first present a deep enhancer screen of a 2-Mbp span covering the IrxA cluster. Using chromosome conformation capture, we show that enhancer sharing is widespread within the cluster, explaining its evolutionarily conserved organization. We also identify a three-dimensional architecture, probably formed through interactions with CCCTC-binding factor, which is present within both Irx clusters of mouse, Xenopus and zebrafish. This architecture brings the promoters of the first two genes together in the same chromatin landscape. We propose that this unique and evolutionarily conserved genomic architecture of the vertebrate Irx clusters is essential for the coregulation of the first two genes and simultaneously maintains the third gene in a partially independent regulatory landscape.
发育基因簇是研究基因调控的典范；然而，介导诸如共调控和增强子共享等现象的机制在很大程度上仍难以捉摸。在这里，我们通过分析脊椎动物 Irx 簇来解决这个问题。我们首先对覆盖 IrxA 簇的 2-Mbp 跨度进行了深入的增强子筛选。使用染色体构象捕获，我们表明增强子共享在簇内广泛存在，解释了其进化上保守的组织。我们还鉴定了一种三维结构，可能是通过与 CCCTC 结合因子的相互作用形成的，这种结构存在于小鼠、非洲爪蟾和斑马鱼的 Irx 簇中。这种结构将前两个基因的启动子在同一染色质景观中聚集在一起。我们提出，脊椎动物 Irx 簇的这种独特且进化上保守的基因组结构对于前两个基因的共调控是必不可少的，同时使第三个基因保持在部分独立的调控景观中。
