During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition.

Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways / Bonnefont, J.; Tiberi, L.; van den Ameele, J.; Potier, D.; Gaber, Z. B.; Lin, X.; Bilheu, A.; Herpoel, A.; Velez Bravo, F. D.; Guillemot, F.; Aerts, S.; Vanderhaeghen, P.. - In: NEURON. - ISSN 0896-6273. - 103:6(2019), pp. 1096-1108.e4. [10.1016/j.neuron.2019.06.027]

Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways

Tiberi L.;
2019-01-01

Abstract

During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition.
2019
6
Bonnefont, J.; Tiberi, L.; van den Ameele, J.; Potier, D.; Gaber, Z. B.; Lin, X.; Bilheu, A.; Herpoel, A.; Velez Bravo, F. D.; Guillemot, F.; Aerts, S.; Vanderhaeghen, P.
Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways / Bonnefont, J.; Tiberi, L.; van den Ameele, J.; Potier, D.; Gaber, Z. B.; Lin, X.; Bilheu, A.; Herpoel, A.; Velez Bravo, F. D.; Guillemot, F.; Aerts, S.; Vanderhaeghen, P.. - In: NEURON. - ISSN 0896-6273. - 103:6(2019), pp. 1096-1108.e4. [10.1016/j.neuron.2019.06.027]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/314789
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