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 language | English (US) |
|---|---|
| Pages (from-to) | 587-601.e7 |
| Journal | Neuron |
| Volume | 102 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 8 2019 |
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Keywords
- demyelination
- differentiation
- myelin
- nuclear pore complex
- nucleoporin
- oligodendrocyte
- Seh1
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination. / Liu, Zhixiong; Yan, Minbiao; Liang, Yaoji; Liu, Min; Zhang, Kun; Shao, Dandan; Jiang, Rencai; Li, Li; Wang, Chaomeng; Nussenzveig, Daniel; Zhang, Kunkun; Chen, Shaoxuan; Zhong, Chuanqi; Mo, Wei; Fontoura, Beatriz M; Zhang, Liang.
In: Neuron, Vol. 102, No. 3, 08.05.2019, p. 587-601.e7.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination
AU - Liu, Zhixiong
AU - Yan, Minbiao
AU - Liang, Yaoji
AU - Liu, Min
AU - Zhang, Kun
AU - Shao, Dandan
AU - Jiang, Rencai
AU - Li, Li
AU - Wang, Chaomeng
AU - Nussenzveig, Daniel
AU - Zhang, Kunkun
AU - Chen, Shaoxuan
AU - Zhong, Chuanqi
AU - Mo, Wei
AU - Fontoura, Beatriz M
AU - Zhang, Liang
PY - 2019/5/8
Y1 - 2019/5/8
N2 - 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.
AB - 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.
KW - demyelination
KW - differentiation
KW - myelin
KW - nuclear pore complex
KW - nucleoporin
KW - oligodendrocyte
KW - Seh1
UR - http://www.scopus.com/inward/record.url?scp=85064999092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064999092&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2019.02.018
DO - 10.1016/j.neuron.2019.02.018
M3 - Article
C2 - 30876848
AN - SCOPUS:85064999092
VL - 102
SP - 587-601.e7
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 3
ER -