Journal
NATURE NEUROSCIENCE
Volume 15, Issue 12, Pages 1627-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3264
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Funding
- Belgian Queen Elizabeth Medical Foundation
- Fondation Pierre Clerdent
- Fondation Roger de Spoelberch
- Action de Recherches Concertees Programs
- Interuniversity Attraction Poles Program, Belgian State, Federal Office for Scientific, Technical and Cultural Affairs
- Belgian FNRS
- Fonds pour la Recherche Scientifique Medicale
- Welbio and Programme d'Excellence CIBLES of the Walloon Region
- EMBO Long-Term Fellowship
- Marie Curie Fellowship
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During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible fate transition to become neurons. The Notch pathway is important for this process, and repression of Notch-dependent Hes genes is essential for triggering differentiation. However, Notch signaling often remains active throughout neuronal differentiation, implying a change in the transcriptional responsiveness to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as encoding a proneurogenic factor that is required for proper neurogenesis of the mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter. BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of the NAD(+)-dependent deacetylase Sirt1, which was required for BCL6-dependent neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal differentiation despite active Notch signaling. Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease.
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