GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells.
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.
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA, 30904, USA.
Yi-Tzang
YT
Tsai
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA, 30904, USA.
Yutaka
Y
Itokazu
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, 30912, USA. ryu@gru.edu.|Charlie Norwood VA Medical Center, Augusta, GA, 30904, USA. ryu@gru.edu.
Robert K
RK
Yu
D000107:Acetylation; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D058105:Polymerization; D011401:Promoter Regions, Genetic
D006657:Histones; D005677:G(M1) Ganglioside; D017350:N-Acetylgalactosaminyltransferases
Brain development; Epigenetic regulation; GM1 ganglioside; Glycosyltransferase; Histone acetylation; Neural progenitor cell; Neural stem cell; Neuronal differentiation