TY - JOUR
T1 - Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells
AU - Itokazu, Yutaka
AU - Tsai, Yi Tzang
AU - Yu, Robert K.
N1 - Publisher Copyright:
© 2016, Springer Science+Business Media New York (outside the USA).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Brain development
KW - DNA methylation
KW - Epigenetics
KW - Ganglioside
KW - Glycosyltransferase
KW - Histone acetylation
KW - Neural stem cell
KW - Neuronal differentiation
KW - Neuronal progenitor cell
UR - http://www.scopus.com/inward/record.url?scp=84982311348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84982311348&partnerID=8YFLogxK
U2 - 10.1007/s10719-016-9719-6
DO - 10.1007/s10719-016-9719-6
M3 - Review article
C2 - 27540730
AN - SCOPUS:84982311348
SN - 0282-0080
VL - 34
SP - 749
EP - 756
JO - Glycoconjugate Journal
JF - Glycoconjugate Journal
IS - 6
ER -