Epigenetic regulation in myelinating glia: The role of histone H2B monoubiquitination in Schwann cells and oligodendrocytes

髓鞘神经胶质细胞的表观遗传调控：组蛋白 H2B 单泛素化在雪旺细胞和少突胶质细胞中的作用

• 批准号: 386610460
• 负责人: Professorin Dr. Elisabeth Sock
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/386610460?language=en
• 关键词: Epigenetic; regulation; myelinating; glia; role

Fast saltatory nerve conduction in the vertebrate nervous system depends on the formation of myelin sheaths around axons by Schwann cells and oligodendrocytes. During development of myelinating glia and the myelination process numerous and substantial epigenetic alterations take place. However, their functions are poorly understood. In this project, I will study the role of core histone H2B monoubiquitination on differentiation of Schwann cells and oligodendrocytes. Using histological, histochemical, ultrastructural und physiological techniques, I will provide an in-depth analysis of the phenotype of mice with specific loss of H2B monoubiquitination in myelin-forming glia. This will be achieved by inactivating the responsible E3 ligase. Using expression profiling and genome-wide chromatin characterization I will determine how loss of H2B monoubiquitination affects glial differentiation and myelination on the molecular level. I will furthermore determine how the underlying mechanism compares between Schwann cells and oligodendrocytes. The comparative identification of the underlying molecular mechanism will lay the groundwork for future studies on therapeutic approaches for dysmyelinating and demyelinating diseases because histone modifications are well accessible to pharmacological intervention.

脊椎动物神经系统的快速跳跃性神经传导依赖于雪旺细胞和少突胶质细胞在轴突周围形成的髓鞘。在髓鞘胶质细胞的发育和髓鞘形成过程中，会发生大量和实质性的表观遗传学变化。然而，人们对它们的功能知之甚少。在这个项目中，我将研究核心组蛋白H_2B单素化在雪旺细胞和少突胶质细胞分化中的作用。利用组织学、组织化学、超微结构和生理学技术，我将深入分析髓鞘形成胶质细胞中H_2B单泛素化特异性丢失的小鼠的表型。这将通过使负责的E3连接酶失活来实现。利用表达谱分析和全基因组染色质表征，我将在分子水平上确定H_2B单泛素化缺失如何影响神经胶质细胞分化和髓鞘形成。我将进一步确定雪旺细胞和少突胶质细胞之间的潜在机制的比较。对潜在分子机制的比较鉴定将为未来研究髓鞘障碍和脱髓鞘疾病的治疗方法奠定基础，因为组蛋白修饰很容易被药物干预。