1. Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination.
- Author
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Liu, Zhixiong, Yan, Minbiao, Liang, Yaoji, Liu, Min, Zhang, Kun, Shao, Dandan, Jiang, Rencai, Li, Li, Wang, Chaomeng, Nussenzveig, Daniel R., Zhang, Kunkun, Chen, Shaoxuan, Zhong, Chuanqi, Mo, Wei, Fontoura, Beatriz M.A., and Zhang, Liang
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MYELINATION , *PROGENITOR cells , *NEUROLOGICAL disorders , *NEURAL development , *OLIGODENDROGLIA - Abstract
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. • Nucleoporin Seh1 is required for OPC differentiation • Seh1 is essential for CNS myelination and remyelination • Seh1 forms a complex with Olig2 at nuclear periphery • Seh1 recruits Olig2 and Brd7 to promote oligodendrocyte development Liu et al. demonstrate that the nucleoporin Seh1 functions in oligodendrocyte differentiation, myelination, and post-injury remyelination by assembling a Seh1/Olig2/Brd7 transcription complex at nuclear periphery. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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