title: An oligodendrocyte enhancer in a phylogenetically conserved intron region of the mammalian myelin gene Opalin.
abstract: Opalin is a transmembrane protein detected specifically in mammalian oligodendrocytes. Opalin homologs are found only in mammals and not in the genome sequences of other animal classes. We first determined the nucleotide sequences of Opalin orthologs and their flanking regions derived from four prosimians, a group of primitive primates. A global comparison revealed that an evolutionarily conserved region exists in the first intron of Opalin. When the conserved domain was assayed for its enhancer activity in transgenic mice, oligodendrocyte-directed expression was observed. In an oligodendroglial cell line, Oli-neu, the conserved domain showed oligodendrocyte-directed expression. The conserved domain is composed of eight subdomains, some of which contain binding sites for Myt1 and cAMP-response element binding protein (CREB). Deletion analysis and cotransfection experiments revealed that the subdomains have critical roles in Opalin gene expression. Over-expression of Myt1, treatment of the cell with leukemia inhibitory factor (LIF), and cAMP analog (CREB activator) enhanced the expression of endogenous Opalin in Oli-neu cells and activated the oligodendrocyte enhancer. These results suggest that LIF, cAMP signaling cascades and Myt1 play significant roles in the differentiation of oligodendrocytes through their action on the Opalin oligodendrocyte enhancer.
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Jun
authors: J
authors: Aruga
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Fumio
authors: F
authors: Yoshikawa
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Yayoi
authors: Y
authors: Nozaki
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Yoshiyuki
authors: Y
authors: Sakaki
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Atsushi
authors: A
authors: Toyoda
authors: Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanLaboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama, JapanSequence Technology Team, RIKEN Genomic Science Center, Yokohama, Japan.
authors: Teiichi
authors: T
authors: Furuichi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D023281:Genomics; D006801:Humans; D007438:Introns / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D011443:Strepsirhini; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D053605:Leukemia Inhibitory Factor; D008156:Luciferases; D009185:Myelin Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C489726:Myt1 protein, mouse; C524020:OPALIN protein, human; C524019:Opalin protein, mouse