Enhancers arecis-regulatory elements which control the expression of genes in a defined spatiotemporal pattern, enabling the normal morphogenesis of organs and structures during embryogenesis. Enhancers control their target genes independently of their orientation or distance through chromosomal looping and are thought to evolve through various mutational mechanisms (1). A critical biological process that leads to the acquisition of new gene expression domains as well as pathological outcomes is termed “enhancer adoption,” whereby a gene is regulated by an enhancer that is not normally its own (2). Enhancer adoption can derive from the insertion of transposable elements (TEs) with regulatory capacities or genomic structural variants (SVs). In particular, many studies have demonstrated the importance of SVs, including deletions, inversions, duplications, and translocations, with regard to 3D genome organization, gene regulation, and disease (3⇓–5). Recent advances in genome engineering and in sequencing technologies have contributed to a deeper understanding of the molecular mechanisms behind genomic rearrangements and their role in evolution and pathology. Therefore, researchers have seized the opportunity to reinterpret old mouse alleles obtained by spontaneous mutations like X-irradiation-induced phocomelia,Hemimelic extra toes(Hx),Ulnaless, and so on, in the light of modern molecular tools (6⇓–8). In PNAS, Mouri et al. (10) set out to reanalyze a mouse mutant with syndactyly and interdigital webbing, known as Hammer toe (Hm), first described in 1964 (9). The authors found that a genomic insertion of an interdigital regulatory region in the vicinity of the geneSonic hedgehog(Shh) results in its ectopic expression and theHmphenotype. The authors use chromatin technologies and CRISPR/Cas9 genetic engineering to dissect the regulatory function of …

中文翻译：

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Shh基因座处的大基因组插入可通过采用增强子来产生锤头

增强子是顺式调节元件，其以限定的时空模式控制基因的表达，使胚胎发生过程中器官和结构的正常形态发生。增强子通过染色体环独立于其方向或距离来控制其靶基因，并被认为是通过各种突变机制进化的（1）。导致获得新基因表达域以及病理结果的关键生物学过程称为“增强子采用”，其中基因受通常不是其自身的增强子调控（2）。增强剂的采用可以源自具有调节能力或基因组结构变异体（SV）的转座因子（TE）的插入。特别是，许多研究已经证明了SV的重要性，包括删除，倒置，3D基因组组织，基因调控和疾病方面的重复和易位（3-5）。基因组工程和测序技术的最新进展使人们对基因组重排背后的分子机制及其在进化和病理学中的作用有了更深入的了解。因此，研究人员抓住了机会，根据现代分子工具，重新解释了由自发突变（例如X射线引起的phocomelia，Hemimelic Extra趾（Hx），Ulnaless等）自发突变获得的旧小鼠等位基因（6⇓-8） 。在PNAS中，Mouri等人。（10）着手重新分析具有突触和趾间织带的小鼠突变体，称为锤头（Hm），最早于1964年描述（9）。作者发现，在基因音速刺猬（Shh）附近插入叉指调控区的基因组会导致其异位表达和两性型。作者使用染色质技术和CRISPR / Cas9基因工程来剖析…的调节功能。