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GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells

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Abstract

Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. We previously demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase) gene promoter resulted in recruitment of trans-activation factors. In addition, we reported that epigenetic activation of the GalNAcT gene was also detected as accompanied by an apparent induction of neuronal differentiation in neural stem cells responding to an exogenous supplement of ganglioside GM1. Here, we present evidence supporting the concept that nuclear GM1 is associated with gene regulation in neuronal cells. We found that nuclear GM1 binds acetylated histones on the promoters of the GalNAcT and NeuroD1 genes in differentiated neurons. Our study demonstrates for the first time that GM1 interacts with chromatin via acetylated histones at the nuclear periphery of neuronal cells.

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Abbreviations

AcH3:

Acetylated histone H3

AcH4:

Acetylated histone H4

ChIP:

Chromatin immunoprecipitation

GalNAcT:

N-acetylgalactosaminyltransferase I (GA2/GM2/GD2/GT2-synthase)

H3K27me3:

Histone H3 with trimethylation on lysine 27

NPC:

Neuronal precursor cell

NSC:

Neural stem cell

ST-II:

Sialyltransferase II (GD3-synthase)

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Acknowledgments

We thank Dr. Wei-Hua Wu for helpful comments on this manuscript. This work was supported in part by a VA Merit Award (1 IO1BX001388 to RKY) and NIH Grants (RO1 NS26994 and RO1 NS11853 to RKY).

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Authors and Affiliations

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

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

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

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

Authors
  1. Yi-Tzang Tsai
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  2. Yutaka Itokazu
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  3. Robert K. Yu
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Corresponding author

Correspondence to Robert K. Yu.

Additional information

Gangliosides are abbreviated using the nomenclatural rules of IUPAC-IUB [1] and according to Svennerholm [2].

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Tsai, YT., Itokazu, Y. & Yu, R.K. GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells. Neurochem Res 41, 107–115 (2016). https://doi.org/10.1007/s11064-015-1742-7

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  • DOI: https://doi.org/10.1007/s11064-015-1742-7

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