Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination

Zhixiong Liu, Minbiao Yan, Yaoji Liang, Min Liu, Kun Zhang, Dandan Shao, Rencai Jiang, Li Li, Chaomeng Wang, Daniel R. Nussenzveig, Kunkun Zhang, Shaoxuan Chen, Chuanqi Zhong, Wei Mo, Beatriz M.A. Fontoura, Liang Zhang

Research output: Contribution to journalArticle

8 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)587-601.e7
JournalNeuron
Volume102
Issue number3
DOIs
StatePublished - May 8 2019

Keywords

  • Seh1
  • demyelination
  • differentiation
  • myelin
  • nuclear pore complex
  • nucleoporin
  • oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Liu, Z., Yan, M., Liang, Y., Liu, M., Zhang, K., Shao, D., Jiang, R., Li, L., Wang, C., Nussenzveig, D. R., Zhang, K., Chen, S., Zhong, C., Mo, W., Fontoura, B. M. A., & Zhang, L. (2019). Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination. Neuron, 102(3), 587-601.e7. https://doi.org/10.1016/j.neuron.2019.02.018