Functional organization of anMbpenhancer exposes striking transcriptional regulatory diversity within myelinating glia
| Autor: | Eric Denarier, Thomas J. Hudson, Bente Finsen, Nancy Dionne, Tanja Kuhlmann, Maia V. Kokoeva, Kathy Siminovitch, Hana Friedman, Régen Drouin, Alan C. Peterson, Samar Dib |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Regulation of gene expression biology Schwann cell Oligodendrocyte Myelin basic protein 03 medical and health sciences Cellular and Molecular Neuroscience Myelin 030104 developmental biology medicine.anatomical_structure nervous system Neurology medicine biology.protein Axon Remyelination Enhancer Neuroscience |
| Zdroj: | Glia. 64:175-194 |
| ISSN: | 0894-1491 |
| Popis: | In mammals, large caliber axons are ensheathed by myelin, a glial specialization supporting axon integrity and conferring accelerated and energy-efficient action potential conduction. Myelin basic protein (MBP) is required for normal myelin elaboration with maximal mbp transcription in oligodendrocytes requiring the upstream M3 enhancer. To further characterize the mechanism regulating mbp transcription, we defined M3 structure/function relationships by evaluating its evolutionary conservation, DNA footprints and the developmental programing conferred in mice by M3 derivatives. Multiple M3 regulatory element combinations were found to drive expression in oligodendrocytes and Schwann cells with a minimal 129 bp sequence conferring expression in oligodendrocytes throughout myelin elaboration, maintenance and repair. Unexpectedly, M3 derivatives conferred markedly different spatial and temporal expression programs thus illuminating striking transcriptional heterogeneity within post-mitotic oligodendrocytes. Finally, one M3 derivative engaged only during primary myelination, not during adult remyelination, demonstrating that transcriptional regulation in the two states is not equivalent. |
| Databáze: | OpenAIRE |
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