Figure 9.

Model for hierarchical reactivation of transcription by Brn2 and Ascl1 in neural stem/progenitor cells undergoing proliferative divisions. Binding of Brn2 to metaphase chromosomes does not involve sequence-specific binding and is mediated by electrostatic interactions. The constant presence near chromatin results in Brn2 inducing the transcriptional reactivation of its target gene Nestin starting from anaphase, a process that requires sequence-specific binding and occurs concomitantly with chromatin decondensation and Brn2 dephosphorylation (events not represented in the figure). In contrast, Ascl1 is excluded from mitotic chromatin, given its low electrostatic potential. Ascl1 concentration in the vicinity of chromatin increases due to nuclear import (upon nuclear envelope reformation), resulting in transcriptional reactivation of its target gene Dll1 in early G1. The different dynamics observed favor an early versus late reactivation of transcriptional targets of Brn2 and Ascl1, respectively.