Co-option of the transcription factor SALL1 in mole ovotestis formation [4C]

Changes in gene expression represent an important source for phenotypical innovation. Yet, how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing comparative analyses of epigenetic and transcriptional data in mole and mouse, we identified SALL1 as a co-opted gene for the formation of testicular tissue in mole ovotestes. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but a prominent evolutionary turnover of enhancer elements. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce the ectopic gene expression programs that are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a prominent mechanism for the evolution of traits. Overall design: We used 4C-seq with the viewpoint in the Sall1 promoter to measure the interacctions of the gene with its regulatory landscape

基因表达变化是表型创新（phenotypical innovation）的重要来源。然而，此类变化如何产生并影响性状演化，迄今尚未明确。
本研究聚焦雌性鼹鼠雄性化卵睾（masculinizing ovotestes）的发育过程，解析其相关分子机制。
通过对鼹鼠与小鼠的表观遗传（epigenetic）及转录组（transcriptional）数据开展比较分析，我们鉴定出SALL1是鼹鼠卵睾中睾丸组织形成的共招募基因。
染色体构象捕获（Chromosome Conformation Capture）分析显示，SALL1基因座的三维（3D）组织结构高度保守，但其增强子元件（enhancer elements）却发生了显著的演化更替。
跨物种报告基因实验（interspecies reporter assays）证实，鼹鼠特异性增强子可在泌尿生殖组织（urogenital tissues）中激活转录。
通过对转基因小鼠（transgenic mice）开展过表达实验，我们进一步证实SALL1可诱导产生鼹鼠卵睾特征性的异位基因表达程序（ectopic gene expression programs）。
本研究结果表明，通过改变增强子活性实现的基因表达共招募，是性状演化的重要机制之一。
实验整体设计：我们采用以Sall1启动子为锚定区域的4C-seq技术，检测该基因与其调控景观之间的相互作用。