The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents

Kunkun Zhang, Shaoxuan Chen, Qihua Yang, Shuanghui Guo, Qiang Chen, Zhixiong Liu, Li Li, Mengyun Jiang, Hongda Li, Jin Hu, Xu Pan, Wenbo Deng, Naian Xiao, Bo Wang, Zhan-xiang Wang (), Liang Zhang () and Wei Mo ()
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Kunkun Zhang: Xiamen University
Shaoxuan Chen: Xiamen University
Qihua Yang: Xiamen University
Shuanghui Guo: Xiamen University
Qiang Chen: Xiamen University
Zhixiong Liu: Xiamen University
Li Li: Xiamen University
Mengyun Jiang: Xiamen University
Hongda Li: Xiamen University
Jin Hu: Xiamen University
Xu Pan: Xiamen University, Xiamen
Wenbo Deng: the First Affiliated Hospital of Xiamen University
Naian Xiao: Xiamen University
Bo Wang: Xiamen University
Zhan-xiang Wang: Xiamen University
Liang Zhang: Xiamen University
Wei Mo: Xiamen University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract OLIG2 is a transcription factor that activates the expression of myelin-associated genes in the oligodendrocyte-lineage cells. However, the mechanisms of myelin gene inactivation are unclear. Here, we uncover a non-canonical function of OLIG2 in transcriptional repression to modulate myelinogenesis by functionally interacting with tri-methyltransferase SETDB1. Immunoprecipitation and chromatin-immunoprecipitation assays show that OLIG2 recruits SETDB1 for H3K9me3 modification on the Sox11 gene, which leads to the inhibition of Sox11 expression during the differentiation of oligodendrocytes progenitor cells (OPCs) into immature oligodendrocytes (iOLs). Tissue-specific depletion of Setdb1 in mice results in the hypomyelination during development and remyelination defects in the injured rodents. Knockdown of Sox11 by siRNA in rat primary OPCs or depletion of Sox11 in the oligodendrocyte lineage in mice could rescue the hypomyelination phenotype caused by the loss of OLIG2. In summary, our work demonstrates that the OLIG2-SETDB1 complex can mediate transcriptional repression in OPCs, affecting myelination.

Date: 2022
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DOI: 10.1038/s41467-022-29068-z

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