Our lab has identified an interesting relation between members of the Myc and E2f family of cell cycle regulators and chromatin changes and transcriptional regulation of differentiation of oligodendrocyte progenitors. We now propose to use primary cultures and genetic mouse models to test a new mechanistic model of oligodendrocyte differentiation. The results from the proposed experimental plan are likely to advance our knowledge not only in neural development and repair, but also in cancer and nuclear reprogramming and have wide implications for the development of novel therapeutic strategies.
The relationship between cell cycle and differentiation in progenitor cells is critical for a vast number of pathologies, ranging from cancer to repair. Although considerable progress has been made in the study of oncogenes in cellular transformation, still very little is known about their role in physiological conditions. This projet defines the role of Myc and E2F in the oligodendrocyte lineage and proposes a novel model of progenitor differentiation, linking cell cycle exit to chromatin condensation and transcriptional modulation.
|Moyon, Sarah; Huynh, Jimmy L; Dutta, Dipankar et al. (2016) Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage. Cell Rep :|
|Moyon, Sarah; Liang, Jialiang; Casaccia, Patrizia (2016) Epigenetics in NG2 glia cells. Brain Res 1638:183-98|
|Liu, Jia; Moyon, Sarah; Hernandez, Marylens et al. (2016) Epigenetic control of oligodendrocyte development: adding new players to old keepers. Curr Opin Neurobiol 39:133-8|
|Hernandez, Marylens; Patzig, Julia; Mayoral, Sonia R et al. (2016) Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes. J Neurosci 36:806-13|
|Liu, Jia; Dupree, Jeffrey L; Gacias, Mar et al. (2016) Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice. J Neurosci 36:957-62|
|Liu, Jia; Magri, Laura; Zhang, Fan et al. (2015) Chromatin landscape defined by repressive histone methylation during oligodendrocyte differentiation. J Neurosci 35:352-65|
|Hernandez, Marylens; Casaccia, Patrizia (2015) Interplay between transcriptional control and chromatin regulation in the oligodendrocyte lineage. Glia 63:1357-75|
|Magri, L; Gacias, M; Wu, M et al. (2014) c-Myc-dependent transcriptional regulation of cell cycle and nucleosomal histones during oligodendrocyte differentiation. Neuroscience 276:72-86|
|Huynh, Jimmy L; Garg, Paras; Thin, Tin Htwe et al. (2014) Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci 17:121-30|
|Magri, Laura; Swiss, Victoria A; Jablonska, Beata et al. (2014) E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation. J Neurosci 34:1481-93|
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