Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliosides are sialic acid-containing glycosphingolipids abundant in the central nervous tissues. The quantity and expression pattern of gangliosides in brain change drastically during early development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. It is still unclear, however, how the transcriptional activation of glycosyltransferase genes is regulated during development. In this study, we investigated the epigenetic regulation of two key glycosyltransferases, N-acetylgalactosaminyltransferase I (GA2/GM2/GD2/GT2-synthase) and sialyltransferase II (GD3-synthase), in embryonic, postnatal, and adult mouse brains. Combined bisulfite restriction analysis assay showed that DNA methylation in the 5' regions of these glycosyltransferase genes was not associated with their expression patterns. On the other hand, chromatin immunoprecipitation assay of both glycosyltransferase genes showed that their histone H3 acetylation was highly correlated to their mRNA expression levels during development. In fact, we confirmed that the expression patterns of gangliosides and glycosyltransferases in neuroepithelial cells were changed after treatment with a histone deacetylase inhibitor, sodium butyrate. Our studies provide the first evidence that efficient histone acetylation of the glycosyltransferase genes in mouse brain contributes to the developmental alteration of ganglioside expression.
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PMID:Histone acetylation-mediated glycosyltransferase gene regulation in mouse brain during development. 2121 66

The quantity and expression pattern of gangliosides in mammalian brain change drastically during development and are mainly regulated through stage-specific expression of ganglioside synthase genes. Despite extensive investigations in the past, it remains largely unclear how the transcriptional activation of the genes encoding glycosyltransferases is regulated. Here, we show that in the neuronogenic cultures of mouse embryonic brain-derived neuroepithelial cells, histone modifications including acetylated histone H3 and histone H4, but not histone H3 trimethylation at lysine 27 of two genes encoding two key regulatory GTs, namely, N-acetylgalactosaminyltransferase I and sialyltransferase II, were extensively and gradually enhanced, respectively. As a consequence, the level of each GT mRNA was increased correspondingly. Hyperacetylation of histones on the GalNAcT promoter resulted in recruitment of the trans-activation factors Sp2 and AP-1 when cellular histone deacetylases 1 and 2 were knocked down with RNA interference or inhibited by treatment with valproic acid. Moreover, epigenetic activation of GalNAcT was also detected, as accompanied by a pronounced induction of neural differentiation in primary neuroepithelium culture responding to an exogenous supplement of ganglioside GM1, a downstream product of the gene's encoding enzyme. Our findings thus provide direct evidence of novel pathways for ganglioside expression via the epigenetic up-regulation of ganglioside synthase genes during neural development.
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PMID:Epigenetic activation of mouse ganglioside synthase genes: implications for neurogenesis. 2410 78