Olig1 Acetylation and Nuclear Export Mediate Oligodendrocyte Development

• Published in: The Journal of neuroscience Vol. 35; no. 48; pp. 15875 - 15893
• Main Authors: Dai, Jinxiang, Bercury, Kathryn K, Jin, Weilin, Macklin, Wendy B
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 02.12.2015
• Subjects: Active Transport, Cell Nucleus - drug effects; Active Transport, Cell Nucleus - genetics; Age Factors; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cells, Cultured; CREB-Binding Protein - genetics; CREB-Binding Protein - metabolism; Embryo, Mammalian; Female; Gene Expression Regulation, Developmental - genetics; Histone Acetyltransferases - metabolism; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation - genetics; Nestin - genetics; Nestin - metabolism; Oligodendroglia - physiology; p300-CBP Transcription Factors - genetics; p300-CBP Transcription Factors - metabolism; Rats; SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; Stem Cells - physiology; acetylation; nuclear export; Olig1
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.0882-15.2015

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.