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Title: BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets
Authors: Tiberi, Luca
van den Ameele, Jelle
Dimidschstein, Jordane
Piccirilli, Julie
Gall, David
Herpoel, Adèle
Bilheu, Angéline
Bonnefont, Jerome
Iacovino, Michelina
Kyba, Michael
Bouschet, Tristan
Vanderhaeghen, Pierre # ×
Issue Date: Dec-2012
Publisher: Nature America Inc.
Series Title: Nature Neuroscience vol:15 issue:12
Article number: 10.1038/nn.3264
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.
URI: 
ISSN: 1097-6256
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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