| First Author | Tiberi L | Year | 2012 |
| Journal | Nat Neurosci | Volume | 15 |
| Issue | 12 | Pages | 1627-35 |
| PubMed ID | 23160044 | Mgi Jnum | J:197487 |
| Mgi Id | MGI:5493185 | Doi | 10.1038/nn.3264 |
| Citation | Tiberi L, et al. (2012) BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets. Nat Neurosci 15(12):1627-35 |
| abstractText | 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. |
