Inhibition of Ezh2 In Vitro and the Decline of <i>Ezh2</i> in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3

Hong, Feng; Zhao, Mengxue; Zhang, Lei; Feng, Linyin

doi:10.1089/scd.2018.0258

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…We observed significant increases in the repressive marks H3K27me3 and H3K9me3 in Pitx3 and Th genes, although significant down-regulation was observed only in Th . Similar observations were recently reported by Hong et al (2019), where they manipulated in vitro the levels of H3K27me3 in the promoter region of Th : treatment with EPZ005687, an inhibitor of histone methylase EZH2 reduces the levels of H3K27me3 and leads to an increase in TH levels; conversely, addition of GSK-J1, which affects the demethylase activity of Jmjd3, augmented H3K27me3 and decreased TH protein levels (Hong et al, 2019). Our data points that not only the H3K27me3 is involved in the regulation of Th , but also H3K9me3 participate.…”

Section: Discussionsupporting

confidence: 82%

Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Vargas-Romero

González‐Barrios

Guerra-Calderas

et al. 2019

Front. Cell. Neurosci.

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During midbrain development, dopamine neuron differentiation occurs before birth. Epigenetic processes such as DNA methylation and demethylation as well as post-translational modification of histones occur during neurogenesis. Here, we administered histamine (HA) into the brain of E12 embryos in vivo and observed significant lower immunoreactivity of Lmx1a+ and Tyrosine Hydroxylase (TH)+ cells, with parallel decreases in the expression of early ( Lmx1a , Msx1) and late ( Th ) midbrain dopaminergic (mDA) genes. With MeDIP assays we found that HA decreases the percentage of 5-methylcytosine of Pitx3 and Th , without changes in 5-hydroxymethylcytosine. Additionally, HA treatment caused a significant increase in the repressive epigenetic modifications H3K9me3 in Pitx3 and Th , and also more H3K27me3 marks in Th . Furthermore, HA has a long-term effect on the formation of the nigrostriatal and mesolimbic/mesocortical pathways, since it causes a significant decrease in midbrain TH immunoreactivity, as well as alterations in dopaminergic neuronal fibers, and significant lower TH-positive area in the forebrain in whole-mount stainings. These findings suggest that HA diminishes dopaminergic gene transcription by altering several epigenetic components related to DNA and histone modifications, which affects mDA neuron progression during development.

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Section: Discussionsupporting

confidence: 82%

Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Vargas-Romero

González‐Barrios

Guerra-Calderas

et al. 2019

Front. Cell. Neurosci.

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“…Epigenetic modifications, such as DNA methylation, histone methylation, and acetylation, are promising therapeutic strategies for the treatment of CVDs (166)(167)(168)(169)(170). Despite the recent advances in epigenetic modifications in CVDs, the potential epigenetic inhibitors for CVD therapy have not been identified.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Yang

Luan

Yuan

et al. 2021

Front. Cardiovasc. Med.

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The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

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“…94,95 Knockdown of EZH2 effectively promotes mdDA neuronal differentiation during midbrain development. 96 Conditional knockout of EZH2 produces ectopic mdDA neurons in the isthmic organizer (IsO) of mice hindbrain. 86 These suggest that PRC2-EZH2 participates in the progress of neural differentiation of stem cells and functional neural structure formation by supporting the generation, maturation and maintenance of differential neural lineage.…”

Section: The Role Of Prc 2 In the Neurog Eni C D Ifferentiati On Of S...mentioning

confidence: 99%

“…Moreover, EZH2 regulates the generation of mesodiencephalic dopaminergic (mdDA) neuron and maintains the proper subset identity and the survival of different mdDA neurons during neural development 94,95 . Knockdown of EZH2 effectively promotes mdDA neuronal differentiation during midbrain development 96 . Conditional knockout of EZH2 produces ectopic mdDA neurons in the isthmic organizer (IsO) of mice hindbrain 86 .…”

Section: The Role Of Prc2 In the Neurogenic Differentiation Of Stem C...mentioning

confidence: 99%

The role and mechanisms of polycomb repressive complex 2 on the regulation of osteogenic and neurogenic differentiation of stem cells

Cao

Fan

2021

Cell Proliferation

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The stem cells differentiate into osteoblasts or neurocytes is the key process for treatment of bone‐ or neural tissue‐related diseases which is caused by ageing, fracture, injury, inflammation, etc Polycomb group complexes (PcGs), especially the polycomb repressive complex 2 (PRC2), act as pivotal epigenetic regulators by modifying key developmental regulatory genes during stem cells differentiation. In this review, we summarize the core subunits, the variants and the potential functions of PRC2. We also highlight the underlying mechanisms of PRC2 associated with the osteogenic and neurogenic differentiation of stem cells, including its interaction with non‐coding RNAs, histone acetyltransferases, histone demethylase, DNA methyltransferase and polycomb repressive complex 1. This review provided a substantial information of epigenetic regulation mediated by PRC2 which leads to the osteogenic and neurogenic differentiation of stem cells.

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Inhibition of Ezh2 In Vitro and the Decline of Ezh2 in Developing Midbrain Promote Dopaminergic Neurons Differentiation Through Modifying H3K27me3

Cited by 5 publications

References 47 publications

Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Histamine Modulates Midbrain Dopamine Neuron Differentiation Through the Regulation of Epigenetic Marks

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

The role and mechanisms of polycomb repressive complex 2 on the regulation of osteogenic and neurogenic differentiation of stem cells

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