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

• Applicant: Professorin Dr. Elisabeth Sock
• Subject Area: Developmental Neurobiology
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 386610460

Myelinating glia ensure saltatory conduction and rapid information processing in the nervous system. Their development and differentiation are subject to epigenetic regulation, including histone modifications. We have shown in the previous funding period that monoubiquitination of histone 2B at lysine 120 (H2Bub1) by the Rnf40-containing E3 ligase is essential for achieving and maintaining a proper myelinated state in Schwann cells of the peripheral nervous system. For that purpose Rnf40 cooperates with Egr2, the master transcriptional regulator of peripheral myelination. We have gathered further evidence, that Rnf40-dependent monoubiquitination is also highly relevant for oligodendrocyte development and function in the central nervous system, however by a different mechanism. In the new funding period, we plan to fully characterize the role of Rnf40 and H2Bub1 in oligodendrocyte differentiation, myelination and in a hitherto unknown communication between myelinating oligodendrocytes and oligodendrocyte progenitor cells. To achieve this we will define the exact phenotypic consequences of oligodendrocyte-specific Rnf40 deletion in mice and identify (i) changes in oligodendroglial gene expression, (ii) direct Rnf40 target genes, (iii) functional interactions of Rnf40 with transcription factors and (iv) Rnf40-sensitive signalling pathways with relevance for oligodendrocyte-to-oligodendrocyte progenitor cell communication. By doing so, our study will yield novel insights into oligodendroglial biology and its epigenetic regulation. It will also be relevant for understanding oligodendrocyte-related pathologies and may eventually be useful for developing therapeutic strategies.

• DFG Programme: Research Grants