par Tiberi, Luca 
;Van Den Ameele, Jelle ;Dimidschstein, Jordane ;Piccirilli, Julie ;Gall, David ;Herpoel, Adèle ;Bilheu, Angeline ;Bonnefont, Jérôme ;Iacovino, Michelina;Kyba, Michael;Bouschet, Tristan ;Vanderhaeghen, Pierre
Référence Nature neuroscience
Publication Publié, 2012-11
;Van Den Ameele, Jelle ;Dimidschstein, Jordane ;Piccirilli, Julie ;Gall, David ;Herpoel, Adèle ;Bilheu, Angeline ;Bonnefont, Jérôme ;Iacovino, Michelina;Kyba, Michael;Bouschet, Tristan ;Vanderhaeghen, Pierre Référence Nature neuroscience
Publication Publié, 2012-11
Article révisé par les pairs
| Résumé : | 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. |
