表观遗传学的可塑性使其成为肿瘤研究以及药物开发的热点。胶质瘤干细胞（GSC）是胶质瘤治疗失败的重要原因，但是其内在的表观遗传紊乱尚不明确。前期研究发现：免疫共沉淀和质谱技术显示GSC中EZH2与HP1BP3存在结合；过表达HP1BP3能够显著增强贴壁胶质瘤细胞耐药能力，且能够抑制H3K9甲基化并上调SOX2表达，升高EZH2则进一步抑制H3K9甲基化水平。敲低HP1BP3后GSC对替莫唑胺的敏感性明显升高。为此我们提出假说：EZH2/HP1BP3复合物通过影响H3K9甲基化促进GSC耐受替莫唑胺。本课题拟证实EZH2/HP1BP3复合物在GSC自我更新和耐药中的作用和机理，建立EZH2/HP1BP3复合物对组蛋白H3K9修饰的精确调控机制，探索EZH2/HP1BP3复合物下游靶基因和信号通路，为胶质瘤发生发展机制提供有益补充，同时为寻找新治疗靶点提供理论依据。

The plasticity of epigenetics makes it a hotspot of cancer research and drug development. Dysregulation of epigenetics in glioma stem cells (GSC), the key of glioma recurrence, remains unclear. Recently, we found that HP1BP3 (Heterochromatin protein 1 binding protein 3) was interacted with EZH2 (enhancer of zeste homolog 2) in GSC through the performance of HPLC-MS/MS and immunoprecipitation experiments. Overexpression of HP1BP3 enhanced the TMZ (temozolomide) resistance in glioma cells. In addition, increased HP1BP3 expression repressed trimethylation of H3K9. HP1BP3 knocked down reversed TMZ resistance in GSC. Thus, EZH2/HP1BP3 complex may regulate TMZ resistance via modulation of H3K9 trimethylation. We plan to determine HP1BP3 expression and function in GSC and clarify the interaction between EZH2 and HP1BP3. Then, we will elucidate the modulation signature of H3K9 trimethylation mediated by EZH2/HP1BP3 complex and investigate the in vivo role of this complex. This study will give us insights into the function and mechanism of H3K9 trimethylation by EZH2/HP1BP3 complex in GSC and explore novel therapy target in glioma treatment.