title: Differential Sox10 genomic occupancy in myelinating glia.
abstract: Myelin is formed by specialized myelinating glia: oligodendrocytes and Schwann cells in the central and peripheral nervous systems, respectively. While there are distinct developmental aspects and regulatory pathways in these two cell types, myelination in both systems requires the transcriptional activator Sox10. Sox10 interacts with cell type-specific transcription factors at some loci to induce myelin gene expression, but it is largely unknown how Sox10 transcriptional networks globally compare between oligodendrocytes and Schwann cells. We used in vivo ChIP-Seq analysis of spinal cord and peripheral nerve (sciatic nerve) to identify unique and shared Sox10 binding sites and assess their correlation with active enhancers and transcriptional profiles in oligodendrocytes and Schwann cells. Sox10 binding sites overlap with active enhancers and critical cell type-specific regulators of myelination, such as Olig2 and Myrf in oligodendrocytes, and Egr2/Krox20 in Schwann cells. Sox10 sites also associate with genes critical for myelination in both oligodendrocytes and Schwann cells and are found within super-enhancers previously defined in brain. In Schwann cells, Sox10 sites contain binding motifs of putative partners in the Sp/Klf, Tead, and nuclear receptor protein families. Specifically, siRNA analysis of nuclear receptors Nr2f1 and Nr2f2 revealed downregulation of myelin genes Mbp and Ndrg1 in primary Schwann cells. Our analysis highlights different mechanisms that establish cell type-specific genomic occupancy of Sox10, which reflects the unique characteristics of oligodendrocyte and Schwann cell differentiation. GLIA 2015;63:1897-1914.
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, 53705.|Comparative Biomedical Sciences Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Camila
authors.initials: C
authors.lastname: Lopez-Anido
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Guannan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Anatomy and Neuroscience and the Centre for Neuroscience Research, University of Melbourne, Melbourne, Australia.
authors.forename: Matthias
authors.initials: M
authors.lastname: Koenning
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Rajini
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, 53705.|Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Hung
authors.affiliation: Department of Anatomy and Neuroscience and the Centre for Neuroscience Research, University of Melbourne, Melbourne, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Emery
authors.affiliation: Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: Sunduz
authors.initials: S
authors.lastname: Keles
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, 53705.|Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, 53705.
authors.forename: John
authors.initials: J
authors.lastname: Svaren
keywords: Schwann; chromatin; enhancer; myelin; oligodendrocyte; transcription