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Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
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Sequentially acting SOX proteins orchestrate astrocyte- and oligodendrocyte-specific gene expression
Susanne Klum1,2, Cécile Zaouter1,2, Zhanna Alekseenko2
1Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden.
EMBO Reports
|September 1, 2018
Summary
SOX transcription factors control glial gene activation. SOX3 prebinds genes in precursors, while SOX9 and SOX10 direct astrocyte and oligodendrocyte development, respectively.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- SOX transcription factors are crucial for glial cell development.
- Mechanisms of glial gene specification and activation remain unclear.
Purpose of the Study:
- To define glial-specific gene expression in the developing spinal cord.
- To elucidate the roles of SOX proteins in glial sub-lineage specification.
Main Methods:
- Single-cell RNA-sequencing to identify glial-specific genes.
- ChIP-sequencing to map SOX protein binding sites.
- Reporter gene assays and functional studies.
Main Results:
- SOX3 prebinds glial gene sets in multipotent neural precursors.
- SOX9 targets astrocyte genes with Nfi binding, while SOX10 targets oligodendrocyte genes.
- SOX3 represses astrocyte gene activation; SOX9 and SOX10 cooperatively activate oligodendrocyte genes.
Conclusions:
- Sequentially expressed SOX proteins orchestrate glial gene expression.
- SOX factors act on lineage-specific regulatory elements for temporal and sub-lineage control.
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