The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents
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...
Saved in:
Published in | Nature communications Vol. 13; no. 1; p. 1423 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
17.03.2022
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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.
Transcription factors regulate gene programs during myelination. Here, the authors show that the Oligodendrocyte Transcription Factor 2 (OLIG2) regulates the differentiation of oligodendrocyte progenitor cells into immature oligodendrocytes via SETDB1 during myelination and remyelination in rodents. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-022-29068-z |