@article{f4ce7c9275a74934af5534e4cf77c627,
title = "Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination",
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.",
keywords = "Seh1, demyelination, differentiation, myelin, nuclear pore complex, nucleoporin, oligodendrocyte",
author = "Zhixiong Liu and Minbiao Yan and Yaoji Liang and Min Liu and Kun Zhang and Dandan Shao and Rencai Jiang and Li Li and Chaomeng Wang and Nussenzveig, {Daniel R.} and Kunkun Zhang and Shaoxuan Chen and Chuanqi Zhong and Wei Mo and Fontoura, {Beatriz M.A.} and Liang Zhang",
note = "Funding Information: We thank Liping Xie, Luming Yao, Caiming Wu, Qingfeng Liu, Changchuan Xie, and Liqiong Yuan for technical support; Guang Li for Venus plasmid; Xin Chen for antibodies; William D. Richardson and Huiliang Li for providing SOX10-CreER T mice; Chong Liu for providing NG2-CreER T mice; and Q. Richard Lu for providing Olig1-Cre mice. This study was funded by grants from the National Natural Science Foundation of China 31872642 (to L.Z.) and 81472725 (to W.M.); the Fundamental Research Funds for the Central Universities 20720160072 (to L.Z. and W.M.); and NIH 1R01 GM113874-01 (to B.M.A.F.). Funding Information: We thank Liping Xie, Luming Yao, Caiming Wu, Qingfeng Liu, Changchuan Xie, and Liqiong Yuan for technical support; Guang Li for Venus plasmid; Xin Chen for antibodies; William D. Richardson and Huiliang Li for providing SOX10-CreERT mice; Chong Liu for providing NG2-CreERT mice; and Q. Richard Lu for providing Olig1-Cre mice. This study was funded by grants from the National Natural Science Foundation of China 31872642 (to L.Z.) and 81472725 (to W.M.); the Fundamental Research Funds for the Central Universities 20720160072 (to L.Z. and W.M.); and NIH 1R01 GM113874-01 (to B.M.A.F.). Conceptualization, L.Z. and W.M.; Methodology, L.Z. W.M. D.R.N. and B.M.A.F.; Investigation, Z.L. M.Y. Kun Zhang, S.C. Kunkun Zhang, R.J. D.S. L.L. C.W. and C.Z.; Formal Analysis, Y.L. M.L. L.Z. and Z.L.; Writing – Original Draft, L.Z.; Writing – Review & Editing, L.Z. and B.M.A.F.; Funding Acquisition, L.Z. W.M. and B.M.A.F.; Supervision, L.Z. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = may,
day = "8",
doi = "10.1016/j.neuron.2019.02.018",
language = "English (US)",
volume = "102",
pages = "587--601.e7",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}