GSE119814
Seh1 Interacts with Olig2 and Brd7 to Promote Oligodendrocyte Differentiation and Myelination (ChIP-Seq)
Nuclear pore complex components (Nups) are involved in neural development and alterations in Nup genes are linked to human neurological diseases. However, the physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here we show that tissue-specific depletion of nucleoporin Seh1 causes dramatic myelination defects in the Central Nervous System (CNS). Seh1-deficient Oligodendrocyte Progenitor Cells (OPCs) proliferate properly, but 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 depletion of Seh1 alters open chromatin configurations at its target genes. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear pores. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and expose nucleoporins as key players in the CNS. Overall design: ChIP was performed on rat oligodendrocyte progenitor cells and immature oligodendrocytes(T3 D1) using antibodies against seh1 or IgG. RNA-seq was performed on mouse control or Seh1cKO immature oligodendrocytes(T3 D2). Atac-seq was performed on mouse control or Seh1cKO oligodendrocyte progenitor cells and immature oligodendrocytes(T3 D1).