Dose-dependent regulation of oligodendrocyte specification by β-catenin signaling

Sun, Shuhui; Guo, Wanshou; Zhang, Zunyi; Qiu, Mengsheng; Dai, Zhong‐Min

doi:10.1007/s12264-014-1513-5

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…This is especially important as we consider the waves of gene regulation (repression and activation) that need to occur to promote myelination. Our discovery of the BHMT-betaine methylation pathway in oligodendrocytes provides insight into how epigenetics, specifically methylation through SAM, can alter DNMT and HMT activity and specifically tailor expression of both positive and negative developmental and remyelination regulators [47][48][49].…”

Section: Plos Onementioning

confidence: 99%

The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation

et al. 2021

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Research into the epigenome is of growing importance as a loss of epigenetic control has been implicated in the development of neurodegenerative diseases. Previous studies have implicated aberrant DNA and histone methylation in multiple sclerosis (MS) disease pathogenesis. We have previously reported that the methyl donor betaine is depleted in MS and is linked to changes in histone H3 trimethylation (H3K4me3) in neurons. We have also shown that betaine increases histone methyltransferase activity by activating chromatin bound betaine homocysteine S-methyltransferase (BHMT). Here, we investigated the role of the BHMT-betaine methylation pathway in oligodendrocytes. Immunocytochemistry in the human MO3.13 cell line, primary rat oligodendrocytes, and tissue from MS postmortem brain confirmed the presence of the BHMT enzyme in the nucleus in oligodendrocytes. BHMT expression is increased 2-fold following oxidative insult, and qRT-PCR demonstrated that betaine can promote an increase in expression of oligodendrocyte maturation genes SOX10 and NKX-2.2 under oxidative conditions. Chromatin fractionation provided evidence of a direct interaction of BHMT on chromatin and co-IP analysis indicates an interaction between BHMT and DNMT3a. Our data show that both histone and DNA methyltransferase activity are increased following betaine administration. Betaine effects were shown to be dependent on BHMT expression following siRNA knockdown of BHMT. This is the first report of BHMT expression in oligodendrocytes and suggests that betaine acts through BHMT to modulate histone and DNA methyltransferase activity on chromatin. These data suggest that methyl donor availability can impact epigenetic changes and maturation in oligodendrocytes.

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Section: Plos Onementioning

confidence: 99%

The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation

et al. 2021

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“…It is interesting that endogenous WNT/β-catenin signaling is activated in newly generated MNs [8]. Activation of WNT/β-catenin signaling has been reported to inhibit the specification of OPCs and astrocytes from NPCs during early stages of gliogenesis [9][10][11]. However, the mechanism underlying the inhibition of OPC specification from pMN NPCs by WNT/βcatenin signaling remains to be determined.…”

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confidence: 99%

WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression

Jiang

Xie

et al. 2020

Mol Brain

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Olig2 transcription factor is essential for the maintenance of neural progenitor cells (NPCs) in the pMN domain and their sequential specification into motor neurons (MNs) and oligodendrocyte precursor cells (OPCs). The expression of Olig2 rapidly declines in newly generated MNs. However, Olig2 expression persists in later-born OPCs and antagonizes the expression of MN-related genes. The mechanism underlying the differential expression of Olig2 in MNs and oligodendrocytes remains unknown. Here, we report that activation of WNT/β-catenin signaling in pMN lineage cells abolished Olig2 expression coupled with a dramatic increase of Ngn2 expression. Luciferase reporter assay showed that Ngn2 inhibited Olig2 promoter activity. Overexpression of Ngn2-EnR transcription repressor blocked the expression of Olig2 in ovo. Our results suggest that down-regulation of WNT-Ngn2 signaling contributes to oligodendrogenesis from the pMN domain and the persistent Olig2 expression in OPCs.

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Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model

Yin,

Luo,

Zhu

et al. 2024

Neurosci. Bull.

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Dose-dependent regulation of oligodendrocyte specification by β-catenin signaling

Cited by 4 publications

References 10 publications

The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation

The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation

WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression

Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model

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