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Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells

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Abstract

The structural diversity and localization of cell surface glycosphingolipids (GSLs), including gangliosides, in glycolipid-enriched microdomains (GEMs, also known as lipid rafts) render them ideally suited to play important roles in mediating intercellular recognition, interactions, adhesion, receptor function, and signaling. Gangliosides, sialic acid-containing GSLs, are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and these changes are mainly regulated through stage-specific expression of glycosyltransferase genes. We previously demonstrated for the first time that efficient histone acetylation of the glycosyltransferase genes in mouse brain contributes to the developmental alteration of ganglioside expression. We further demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase; B4galnt1) gene promoter resulted in recruitment of trans-activation factors. In addition, we showed that epigenetic activation of the GalNAcT gene was detected and accompanied by an apparent induction of neuronal differentiation of neural stem cells (NSCs) responding to an exogenous supplement of ganglioside GM1. Most recently, we found that nuclear GM1 binds with acetylated histones on the promoters of the GalNAcT as well as on the NeuroD1 genes in differentiated neurons. Here, we will introduce epigenetic regulation of ganglioside synthase genes in neural development and neuronal differentiation of NSCs.

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Acknowledgments

This work was supported in part by a VA Merit Review Award (1 IO1BX001388 to RKY), NIH grants (RO1 NS26994 and RO1 NS11853 to RKY) and Mizutani Foundation for Glycoscience (150026 to YI).

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Authors and Affiliations

  1. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA

    Yutaka Itokazu, Yi-Tzang Tsai & Robert K. Yu

  2. Charlie Norwood VA Medical Center, Augusta, GA, 30904, USA

    Yutaka Itokazu, Yi-Tzang Tsai & Robert K. Yu

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  1. Yutaka Itokazu
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  2. Yi-Tzang Tsai
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  3. Robert K. Yu
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Correspondence to Robert K. Yu.

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Itokazu, Y., Tsai, YT. & Yu, R.K. Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells. Glycoconj J 34, 749–756 (2017). https://doi.org/10.1007/s10719-016-9719-6

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