Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations. Chromatin conformation analysis revealed that these enhancers and transcription factors form distinct architectures within these lineages in the spinal cord. In glioma models, the glia-specific architecture is present in tumors, and these enhancers are required for NFIA expression and contribute to glioma formation. By delineating three-dimensional mechanisms of gene expression regulation, our studies identify lineage-specific chromatin architectures and associated enhancers that regulate cell fate and tumorigenesis in the CNS.

中文翻译：

---

胶质细胞特异性增强子和染色质结构调节NFIA的表达和神经胶质瘤的肿瘤发生。

远程增强子的相互作用关键性地调节基因表达，但人们对其协同活动如何促进中枢神经系统发育或与疾病状态的关系知之甚少。通过检查发育中的脊髓中转录因子NFIA的调节，我们鉴定了在体内通过胶质和神经元谱系概括NFIA表达的远程增强子。补充遗传研究发现，Sox9-Brn2和Isl1-Lhx3调节神经胶质和神经元人群中的增强子活性和NFIA表达。染色质构象分析表明，这些增强子和转录因子在脊髓的这些谱系内形成了独特的结构。在神经胶质瘤模型中，神经胶质细胞特异性结构存在于肿瘤中，这些增强子是NFIA表达所必需的，并有助于神经胶质瘤的形成。通过描绘基因表达调控的三维机制，我们的研究确定了谱系特异性的染色质结构和相关的增强子，它们调节中枢神经系统的细胞命运和肿瘤发生。