Laboratory for Mouse Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.
Dev Growth Differ. 2020 Jun;62(5):355-362. doi: 10.1111/dgd.12671. Epub 2020 May 30.
The mammalian Dlx genes encode homeobox-type transcription factors and are physically organized as convergent bigene clusters. The paired Dlx genes share tissue specificity in the expression profile. Genetic regulatory mechanisms, such as intergenic enhancer sharing between paired Dlx genes, have been proposed to explain this conservation of bigene structure. All mammalian Dlx genes have expression and function in developing craniofacial structures, especially in the first and second pharyngeal arches (branchial arches). Each Dlx cluster (Dlx1/2, Dlx3/4, and Dlx5/6) has overlapping, nested expression in the branchial arches which is called the "Dlx code" and plays a key role in organizing craniofacial structure and evolution. Here we summarize cis-regulatory studies on branchial arch expression of the three Dlx bigene clusters and show some shared characteristics among the clusters, including cis-regulatory motifs, TAD (Topologically Associating Domain) boundaries, CTCF loops, and distal enhancer landscapes, together with a molecular condensate model for activation of the Dlx bigene cluster.
哺乳动物的 Dlx 基因编码同源盒型转录因子，并且在物理上组织为会聚的双基因簇。成对的 Dlx 基因在表达谱中具有组织特异性。遗传调控机制，例如配对 Dlx 基因之间的基因间增强子共享，被提出解释这种双基因结构的保守性。所有哺乳动物的 Dlx 基因都在发育中的颅面结构中表达和发挥功能，特别是在第一和第二咽弓（鳃弓）中。每个 Dlx 簇（Dlx1/2、Dlx3/4 和 Dlx5/6）在鳃弓中具有重叠的嵌套表达，称为“Dlx 代码”，在组织颅面结构和进化中起着关键作用。在这里，我们总结了三个 Dlx 双基因簇在鳃弓表达的顺式调控研究，并展示了簇之间的一些共同特征，包括顺式调控基序、TAD（拓扑关联域）边界、CTCF 环和远端增强子景观，以及激活 Dlx 双基因簇的分子凝聚物模型。
