Nat Neurosci 2012,
PMID: 23160044
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
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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Text Mining Data
neuronal differentiation ⊣ Hes5: "
The resulting epigenetic silencing of
Hes5 led to
neuronal differentiation despite active Notch signaling
"
Notch-BCL6-Sirt1 ⊣ BCL6: "
Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease
"
Notch-BCL6-Sirt1 ⊣ BCL6: "
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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