title: Olig1 Acetylation and Nuclear Export Mediate Oligodendrocyte Development.
abstract: The oligodendrocyte transcription factor Olig1 is critical for both oligodendrocyte development and remyelination in mice. Nuclear to cytoplasmic translocation of Olig1 protein occurs during brain development and in multiple sclerosis, but the detailed molecular mechanism of this translocation remains elusive. Here, we report that Olig1 acetylation and deacetylation drive its active translocation between the nucleus and the cytoplasm in both mouse and rat oligodendrocytes. We identified three functional nuclear export sequences (NES) localized in the basic helix-loop-helix domain and one specific acetylation site at Lys 150 (human Olig1) in NES1. Olig1 acetylation and deacetylation are regulated by the acetyltransferase CREB-binding protein and the histone deacetylases HDAC1, HDAC3, and HDAC10. Acetylation of Olig1 decreased its chromatin association, increased its interaction with inhibitor of DNA binding 2 and facilitated its retention in the cytoplasm of mature oligodendrocytes. These studies establish that acetylation of Olig1 regulates its chromatin dissociation and subsequent translocation to the cytoplasm and is required for its function in oligodendrocyte maturation.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045.
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Bercury
authors.affiliation: Institute of Bio-Nano-Science and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045, Wendy.Macklin@ucdenver.edu.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D064231:Nestin; D055757:SOXE Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C577485:Nes protein, mouse; C494786:Olig1 protein, mouse; C527924:Sox10 protein, mouse
keywords: Olig1; acetylation; nuclear export