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

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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.