BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets - PubMed (original) (raw)

. 2012 Dec;15(12):1627-35.

doi: 10.1038/nn.3264. Epub 2012 Nov 18.

Jelle van den Ameele, Jordane Dimidschstein, Julie Piccirilli, David Gall, Adèle Herpoel, Angéline Bilheu, Jerome Bonnefont, Michelina Iacovino, Michael Kyba, Tristan Bouschet, Pierre Vanderhaeghen

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

Luca Tiberi et al. Nat Neurosci. 2012 Dec.

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.

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