A Novel Glioma-specific Enhancer Maintains Glioma Temozolomide Sensitivity By Regulation of RasGRP3 Expression via Long-range Chromosome Interactions

In this study, we report the identification of a glioma-specific enhancer that confers sensitivity to TMZ by upregulation of the mitogen-associated protein kinase activator RasGRP3. Deletion of either the active domain of RasGPR3 or the enhancer using CRISPR/Cas9, was sufficient to restore sensitivity to TMZ in a resistant population of cells that was reversed with overexpression of RasGRP3. The project include RNA-seq, Hi-C, Capture Hi-C between DMSO-treated U251 and TMZ-treated U251. RNA-seq, Hi-C, Capture Hi-C between DMSO-treated U251 and TMZ-treated U251

本研究鉴定出一种胶质瘤特异性增强子，该增强子通过上调丝裂原活化蛋白激酶（mitogen-associated protein kinase, MAPK）激活因子RasGRP3，赋予细胞对替莫唑胺（TMZ）的敏感性。利用CRISPR/Cas9技术敲除RasGRP3的活性结构域或该增强子，即可在耐药细胞群中恢复对TMZ的敏感性，该表型可通过过表达RasGRP3得以逆转。本项目包含经二甲基亚砜（DMSO）处理的U251细胞与经TMZ处理的U251细胞的RNA测序（RNA-seq）、Hi-C及捕获Hi-C（Capture Hi-C）实验，且该检测方案已重复执行一次。