Sequentially acting SOX proteins orchestrate astrocyte‐ and oligodendrocyte‐specific gene expression. (30th August 2018)

• Record Type: Journal Article
• Authors: Klum, Susanne; Zaouter, Cécile; Alekseenko, Zhanna; Björklund, Åsa K; Hagey, Daniel W; Ericson, Johan; Muhr, Jonas; Bergsland, Maria
• Is Part Of: EMBO reports. Volume 19:Number 11(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-08-30
• Subjects: ChIP‐seq -- gliogenesis -- prebinding -- single‐cell RNA‐sequencing -- SOX proteins; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201846635
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: 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. Synopsis: By single‐cell RNA‐seq and ChIP‐seq analyses this study defines gene expression in spinal cord gliogenesis and reveals how sequentially expressed SOX proteins control glial gene expression in a temporal and sub‐lineage specific fashion. Astrocyte‐ and oligodendrocyte‐specific gene expression is defined in the developing mouse spinal cord. SOX3 and SOX9 preselect gene programs in NPCs and GPCs that are first activated during gliogenesis. Temporal onset of astrocyte gene expression is coordinated by SOX3‐mediated repression of SOX9 activation. Abstract : By single‐cell RNA‐seq and ChIP‐seq analyses this study defines gene expression in spinal cord gliogenesis and reveals how sequentially expressed SOX proteins control glial gene expression in a temporal and sub‐lineage specific fashion.