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Functional Analysis of Histone Demethylase Jmjd2b on Lipopolysaccharide-Treated Murine Neural Stem Cells (NSCs)

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Abstract

Neural stem cell (NSC) neurogenesis is the formation of new neurons by which the brain maintains its lifelong plasticity in response to extrinsic and intrinsic changes. Here, we show the effect of lipopolysaccharides (LPS) as an in vitro model of inflammation on NSCs to determine whether the inflammatory mediators can epigenetically affect NSCs and alter their proliferation and differentiation abilities. To study the effect of LPS on NSCs, we used an immortalized mouse neuroectodermal stem cell line, NE-4C. We found that Jmjd2b, histone-3 lysine-9 di-/tri-methyl (H3K9me2/3) demethylase, is functional following LPS treatment and is crucial in multiple signaling pathways and biological processes. The global gene expression levels were detected in Jmjd2b-knockdown (kd) NE-4C cells and in LPS-stimulated Jmjd2b-kd NE-4C cells using an Affymetrix GeneChip® Mouse Gene 1.0 ST Array. In addition, the datasets were analyzed using MetaCore Pathway Analysis (GeneGo). The attenuation of Jmjd2b in NE-4C cells significantly affected the p65, iNOS, Bcl2, and TGF-β expression levels and had downstream effects on related signaling pathways. In addition, chromatin immunoprecipitation revealed that Jmjd2b-kd could inhibit the Notch1, IL-1β, and IL-2 genes by recruiting repressive H3K9me3 to their promoters. Moreover, this study highlights Jmjd2b role in LPS-mediated inflammation, which suggests an epigenetic regulation in NE-4C cells. Finally, this study establishes novel Jmjd2b targets that potentiate a biological rationale involving Jmjd2b in NSC inflammation.

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Acknowledgments

This work was supported by grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs (A101712), and the National Research Foundation of Korea (No. 2011-0030768); Republic of Korea.

Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Molecular & Life Science, Hanyang University, 1271 Sa 3-dong, Gyeonggi-do, Ansan, 426-791, Korea

    Nando Dulal Das, Mi Ran Choi, Kyoung Hwa Jung, Ji Hyun Park, Hyung Tae Lee, Amitabh Das & Young Gyu Chai

  2. Department of Neurology, Hanyang University, Seoul, 133-792, Korea

    Seung Hyun Kim

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  1. Nando Dulal Das
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  2. Mi Ran Choi
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Correspondence to Young Gyu Chai.

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Das, N.D., Choi, M.R., Jung, K.H. et al. Functional Analysis of Histone Demethylase Jmjd2b on Lipopolysaccharide-Treated Murine Neural Stem Cells (NSCs). Neurotox Res 23, 154–165 (2013). https://doi.org/10.1007/s12640-012-9346-3

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  • DOI: https://doi.org/10.1007/s12640-012-9346-3

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