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Sequentially acting SOX proteins orchestrate astrocyte‐ and oligodendrocyte‐specific gene expression
Author(s) -
Klum Susanne,
Zaouter Cécile,
Alekseenko Zhanna,
Björklund Åsa K,
Hagey Daniel W,
Ericson Johan,
Muhr Jonas,
Bergsland Maria
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846635
Subject(s) - astrocyte , biology , gene expression , gene , microbiology and biotechnology , regulation of gene expression , oligodendrocyte , protein expression , genetics , computational biology , neuroscience , myelin , central nervous system
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 Ch IP ‐seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX 3. In the subsequent lineage‐restricted glial precursor cells, astrocyte genes become additionally targeted by SOX 9 at DNA regions strongly enriched for Nfi binding motifs. Oligodendrocyte genes instead are prebound by SOX 9 only, at sites which during oligodendrocyte maturation are targeted by SOX 10. Interestingly, reporter gene assays and functional studies in the spinal cord reveal that SOX 3 binding represses the synergistic activation of astrocyte genes by SOX 9 and NFIA , whereas oligodendrocyte genes are activated in a combinatorial manner by SOX 9 and SOX 10. 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.