Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia
| Autor: | Dionne, Nancy, Dib, Samar, Finsen, Bente, Denarier, Eric, Kuhlmann, Tanja, Drouin, Régen, Kokoeva, Maia, Hudson, Thomas J, Siminovitch, Kathy, Friedman, Hana C, Peterson, Alan C |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Molecular Sequence Data Avian Proteins/genetics Mice Transgenic Sciatic Nerve/growth & development Optic Nerve/growth & development Myelin Sheath/genetics Myelin repair Animals Gene Regulatory Networks Spinal Cord/growth & development In Situ Hybridization Conserved Sequence Base Sequence Myelin Basic Protein/genetics Oligodendrocyte Immunohistochemistry Schwann cell Gene regulation nervous system Myelin beta-Galactosidase/metabolism Mutation Brain/growth & development Sequence Alignment Chickens |
| Zdroj: | Dionne, N, Dib, S, Finsen, B, Denarier, E, Kuhlmann, T, Drouin, R, Kokoeva, M, Hudson, T J, Siminovitch, K, Friedman, H C & Peterson, A C 2016, ' Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia ', Glia, vol. 64, no. 1, pp. 175–194 . https://doi.org/10.1002/glia.22923 |
| DOI: | 10.1002/glia.22923 |
| 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. GLIA 2015. |
| Databáze: | OpenAIRE |
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