The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents.
Kunkun ZhangShaoxuan ChenQihua YangShuanghui GuoQiang ChenZhi-Xiong LiuLi LiMengyun JiangHongda LiJin HuXu PanWenbo DengNaian XiaoBo WangZhan-Xiang WangLiang ZhangWei MoPublished in: Nature communications (2022)
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.
Keyphrases
- transcription factor
- genome wide identification
- dna binding
- poor prognosis
- genome wide
- induced apoptosis
- copy number
- high fat diet induced
- gene expression
- single cell
- white matter
- oxidative stress
- high throughput
- multiple sclerosis
- dna damage
- binding protein
- dna methylation
- cell cycle arrest
- metabolic syndrome
- drug delivery
- cell proliferation
- protein kinase
- skeletal muscle
- hyaluronic acid