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Sequentially acting SOX proteins orchestrate astrocyte- and oligodendrocyte-specific gene expression
Karolinska Inst, Ludwig Inst Canc Res, Stockholm, Sweden;Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
Karolinska Inst, Ludwig Inst Canc Res, Stockholm, Sweden;Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-2224-7090
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2018 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 19, no 11, article id e46635Article in journal (Refereed) Published
Abstract [en]

SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, by ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA regions strongly enriched for Nfi binding motifs. Oligodendrocyte genes instead are prebound by SOX9 only, at sites which during oligodendrocyte maturation are targeted by SOX10. Interestingly, reporter gene assays and functional studies in the spinal cord reveal that SOX3 binding represses the synergistic activation of astrocyte genes by SOX9 and NFIA, whereas oligodendrocyte genes are activated in a combinatorial manner by SOX9 and SOX10. These genome-wide studies demonstrate how sequentially expressed SOX proteins act on lineage-specific regulatory DNA elements to coordinate glial gene expression both in a temporal and in a sub-lineage-specific fashion.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 19, no 11, article id e46635
Keywords [en]
ChIP-seq, gliogenesis, prebinding, single-cell RNA-sequencing, SOX proteins
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-371091DOI: 10.15252/embr.201846635ISI: 000449752600018PubMedID: 30166336OAI: oai:DiVA.org:uu-371091DiVA, id: diva2:1272720
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Cancer SocietyAvailable from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-01-07Bibliographically approved

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Björklund, Åsa K.

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