Histone acetylation-mediated glycosyltransferase gene regulation in mouse brain during development

Yusuke Suzuki, Makoto Yanagisawa, Toshio Ariga, Robert K. Yu

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)874-880
Number of pages7
JournalJournal of Neurochemistry
Volume116
Issue number5
DOIs
StatePublished - Mar 2011

Keywords

  • DNA methylation
  • epigenetics
  • gangliosides
  • glycosyltransferase
  • histone acetylation
  • neural stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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