脑胶质瘤中ATRX是诊断分型、预后判断的重要分子标记物。申请人前期利用Hi-C、ChIP-seq及RNA表达谱等技术发现ATRX可影响染色质三维结构，与PDGFRA和NEAT1表达相关，抑制EZH2降解，介导组蛋白修饰，调控脑胶质瘤干细胞干性。在此基础上，拟利用Hi-C和高通量染色质免疫共沉淀等相关技术，揭示ATRX促进PDGFRA转录，调控脑胶质瘤干细胞干性的具体机制；明确ATRX抑制EZH2泛素化降解对基因组表观遗传修饰的调控作用；进一步分析ATRX介导NEAT1/组蛋白修饰复合体促进脑胶质瘤干细胞干性的调节模式；利用特异性PDGFRA抑制剂和EZH2抑制剂研究ATRX表达型脑胶质瘤干细胞干性的抑制作用方式。本研究可揭示ATRX调控染色质三维结构改变和组蛋白修饰促进脑胶质瘤干细胞干性的作用机制，有望为脑胶质瘤个体化治疗和临床标记物的发现提供新途径。

ATRX plays an important role in glioma diagnosis and prognosis. Previously, we utilized Hi-C, ChIP-seq and GEP to find that ATRX could alternate 3D chromatin architecture, correlate with PDGFRA and NEAT1 expression, and mediate glioma epigenetic signature by inhibiting EZH2 degradation. On these basis, we aim to explore the mechanism underneath ATRX maintains glioma stemness through regulating PDGFRA transcription. We will ascertain the function of ATRX-related histone modification by regulating EZH2 degradation and clarify the molecular mechanism of ATRX mediated NEAT1/histone modification complex in regulating glioma stem cell signaling pathway and promoting glioma stemness. Finally, we will carry out the specific antagonistic inhibitors of PDGFRA and EZH2 to assess the inhibitory effect on glioma stemness. This study will contribute to revealing the effect of ATRX on 3D chromatin architecture, histone modification and down-stream regulation network in glioma, which is intended to provide a theoretical evidence in clinical marker excavation and individual treatment in glioma.