Nucleoporins (Nups) are involved in neural development, and alterations in Nup genes are linked to human neurological diseases. However, physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here, we show that tissue-specific depletion of the nucleoporin Seh1 causes dramatic myelination defects in the CNS. Although proliferation is not altered in Seh1-deficient oligodendrocyte progenitor cells (OPCs), they fail to differentiate into mature oligodendrocytes, which impairs myelin production and remyelination after demyelinating injury. Genome-wide analyses show that Seh1 regulates a core myelinogenic regulatory network and establishes an accessible chromatin landscape. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear periphery. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and define a nucleoporin as a key player in the CNS.
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| http://dx.doi.org/10.1016/j.neuron.2019.02.018 | DOI Listing |
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Article Synopsis
- Schwann cells are crucial for nerve function, but how they maintain balance is not well understood; this study highlights the role of a protein called Seh1 in their stability.
- As mice age, Seh1 levels drop, leading to immune activation and cell death when it's lost, resulting in fewer Schwann cells and nerve issues.
- Seh1 helps keep the genome stable by connecting two other proteins, and without it, harmful elements can activate cell death in Schwann cells, suggesting that changes in nucleoporins could contribute to nerve diseases.
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