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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS052738-06A1
Application #
8319125
Study Section
Special Emphasis Panel (ZRG1-MDCN-N (02))
Program Officer
Owens, David F
Project Start
2007-06-15
Project End
2016-02-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
6
Fiscal Year
2012
Total Cost
$370,781
Indirect Cost
$152,031
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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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