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Nat Neurosci. 2012 Dec;15(12):1627-35. doi: 10.1038/nn.3264. Epub 2012 Nov 18.

BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets.

Author information

1
Université Libre de Bruxelles, Institute for Interdisciplinary Research, ULB Neuroscience Institute, Brussels, Belgium.

Abstract

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.

PMID:
23160044
DOI:
10.1038/nn.3264
[Indexed for MEDLINE]

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