title: Brain-specific expression of N-acetylglucosaminyltransferase IX (GnT-IX) is regulated by epigenetic histone modifications.
abstract: It is well known that biosynthesis of glycans takes place in organ- and tissue-specific manners and glycan expression is controlled by various factors including glycosyltransferases. The expression mechanism of glycosyltransferases, however, is poorly understood. Here we investigated the expression mechanism of a brain-specific glycosyltransferase, GnT-IX (N-acetylglucosaminyltransferase IX, also designated as GnT-Vb), which synthesizes branched O-mannose glycan. Using an epigenetic approach, we revealed that the genomic region around the transcriptional start site of the GnT-IX gene was highly associated with active chromatin histone marks in a neural cell-specific manner, indicating that brain-specific GnT-IX expression is under control of an epigenetic "histone code." By EMSA and ChIP analyses we identified two regulatory proteins, NeuroD1 and CTCF that bind to and activate the GnT-IX promoter. We also revealed that GnT-IX expression was suppressed in CTCF- and NeuroD1-depleted cells, indicating that a NeuroD1- and CTCF-dependent epigenetic mechanism governs brain-specific GnT-IX expression. Several other neural glycosyltransferase genes are also found to be regulated by epigenetic histone modifications. This is the first report demonstrating a molecular mechanism at the chromatin level underlying tissue-specific glycan expression.
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Advanced Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D000076246:CCCTC-Binding Factor; D044127:Epigenesis, Genetic / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins; D014157:Transcription Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000076246:CCCTC-Binding Factor; D006657:Histones; D017351:N-Acetylglucosaminyltransferases; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C501008:Neurod1 protein, mouse; C510765:N-acetylglucosaminyltransferase IX, mouse