GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells

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.

Gangliosides in Nerve Cell Specification

“…107 Our confocal microscopy study reveals that nuclear GM1 is colocalized with lamin B1 (a protein of the nuclear lamina) or nucleoporin (a protein of the nuclear pore complex) on the nuclear periphery of induced neurons from NSCs. 40 Coimmunoprecipitation experiments show that nuclear GM1 interacts with AcH3 and AcH4, both active epigenetic marks, but not with H3K27me3, an inactive epigenetic mark. Chromatin immunoprecipitation assays reveal that the promoter regions of the GM2/GD2S and NeuroD1 genes are associated with GM1.…”

“…This result suggests that the interaction of GM1 and the GM2/GD2S gene promoter occurs in a differentiation stage-specific manner. 40 …”

“…39 More recently, we found that nuclear GM1 binds with acetylated histones on the promoters of the GM2/GD2S gene as well as on the neurogenic transcription factor, NeuroD1 gene, in differentiated neurons. 40 Here, we will further discuss the importance of ganglioside regulation in neural development and neuronal differentiation of NSCs.…”

Translation of genome to glycome: role of the Golgi apparatus

“…Several studies have demonstrated a change in expression of glycogenes in response to cell intrinsic or extrinsic factors . For instance, epigenetic mechanisms have been shown to regulate the changes in glycogene expression that leads to a switch from neutral globo and lacto series GSLs to acidic ganglio‐series GSLs during neuronal differentiation . Similar mechanisms have also been shown to regulate transcription of glycogenes producing tumor‐related glycans likely supporting malignant transformation .…”

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

“…Further, we have demonstrated that acetylation of histones H3 and H4 on the GalNAcT gene promoter leads to recruitment of trans-activation factors SP1 and AP-2 [9]. More recently, we found that nuclear GM1 binds with acetylated histones on the promoters of the GalNAcT as well as on the neurogenic transcription factor, NeuroD1 gene, in differentiated neurons [23]. Here, we will further elaborate the importance of epigenetic regulation of ganglioside synthase genes in neural development and neuronal differentiation of NSCs.…”