Thursday, 10 December 2015

Oligodendrocyte protein function is controlled by epigenetics

Olig1 Acetylation and Nuclear Export Mediate Oligodendrocyte Development. Dai J, Bercury KK, Jin W, Macklin WB.
J Neurosci. 2015 Dec 2;35(48):15875-93. 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.
SIGNIFICANCE STATEMENT:
The nuclear to cytoplasmic translocation of Olig1 protein has been observed during mouse and human brain development and in multiple sclerosis in several studies, but the detailed molecular mechanism of this translocation remains elusive. Here, we provide insight into the mechanism by which acetylation (
is the process where an acetyl functional group is transferred from one molecule to another. Deacetylation is simply the reverse reaction where an acetyl group is removed from a molecule).of Olig1 regulates its unique nuclear-cytoplasmic shuttling during oligodendrocyte development and how the acetylation status of Olig1 modulates its distinct function in the nucleus versus the cytoplasm. The current study provides a unique example of a lineage-specific transcription factor that is actively translocated from the nucleus to the cytoplasm as the cell differentiates. Importantly, we demonstrate that this process is tightly controlled by acetylation at a single lysine.

Apologise I don't have time to explain this one, so it may be of interest to the people in the know and for those not in the known it is not a big deal if you don't understand this but it is all about oligodendrocyte function. The more we know the easier it will be to may remyelination happen.

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