Abstract Sox10 belongs to the Sox family of high-mobility group-box transcription factors. It fulfils widespread and essential functions in myelinating glia at multiple stages of development such as glial specification, survival and terminal differentiation. To a large extent, these diverse activities can be attributed to its capacity to interact with different transcription factors in distinct regulatory networks. Beyond transcription factors, an increasing number of interaction partners are emerging with alternative impact on gene expression. These include components of the mediator complex, the Brahma-associated factor complex and histone deacetylases. Here, we discuss interactions with functional relevance in myelinating glia and link Sox10 function in these cells not only to gene transcription, but also to epigenetics and chromatin remodeling.