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During cell division, drastic cellular changes characteristic of mitosis result in the inactivation of the transcriptional machinery, and global downregulation of transcription. Sequence-specific transcription factors (TFs) have thus been considered mere bystanders, devoid of any regulatory function during mitosis. This view changed significantly in recent years, upon the conclusion that many TFs associate with condensed chromosomes during cell division, even occupying a fraction of their genomic target sites in mitotic chromatin. This finding was at the origin of the concept of mitotic bookmarking by TFs, proposed as a mechanism to propagate gene regulatory information across cell divisions, by facilitating the reactivation of specific bookmarked genes. While the underlying mechanisms and biological significance of this model remain elusive, recent developments in this fast-moving field have cast new light into TF activity during mitosis, beyond a bookmarking role. Here, we start by reviewing the most recent findings on the complex nature of TF–chromatin interactions during mitosis, and on mechanisms that may regulate them. Next, and in light of recent reports describing how transcription is reinitiated in temporally distinct waves during mitosis-to-G1 transition, we explore how TFs may contribute to defining this hierarchical gene expression process. Finally, we discuss how TF activity during mitotic exit may impact the acquisition of cell identity upon cell division, and propose a model that integrates dynamic changes in TF–chromatin interactions during this cell-cycle period, with the execution of cell-fate decisions.

Proneural genes were initially identified in Drosophila, where pioneer work on these important regulators of neural development was performed, and from which the term proneural function was coined. Subsequently, their counterparts in vertebrates were identified, and their function in neural development extensively characterized. The function of proneural transcription factors in flies and vertebrates is, however, very distinct. In flies, proneural genes play an early role in neural induction, by endowing neural competence to ectodermal cells. In contrast, vertebrate proneural genes are expressed only after neural specification, in neural stem and progenitor cells, where they play key regulatory functions in quiescence, proliferation, and neuronal differentiation. An exception to this scenario is the Drosophila proneural gene asense, which has a late onset of expression in neural stem cells of the developing embryo and larvae, similar to its vertebrate counterparts. Although the role of Asense remains poorly investigated, its expression pattern is suggestive of functions more in line with those of vertebrate proneural genes. Here, we revise our current understanding of the multiple activities of Asense and of its closest vertebrate homologue Ascl1 in neural stem/progenitor cell biology, and discuss possible parallels between the two transcription factors in neurogenesis regulation.

Cadherins are calcium-binding proteins with a pivotal role in cell adhesion and tissue homeostasis. The cadherin-dependent mechanisms of cell adhesion and migration are exploited by cancer cells, contributing to tumor invasiveness and dissemination. In particular, cadherin switch is a hallmark of epithelial to mesenchymal transition, a complex development process vastly described in the progression of most epithelial cancers. This is characterized by drastic changes in cell polarity, adhesion, and motility, which lead from an E-cadherin positive differentiated epithelial state into a dedifferentiated mesenchymal-like state, prone to metastization and defined by N-cadherin expression. Although vastly explored in epithelial cancers, how these mechanisms contribute to the pathogenesis of other non-epithelial tumor types is poorly understood. Herein, the current knowledge on cadherin expression in normal development in parallel to tumor pathogenesis is reviewed, focusing on epithelial to mesenchymal transition. Emphasis is taken in the unascertained cadherin expression in CNS tumors, particularly in gliomas, where the potential contribution of an epithelial-to-mesenchymal-like process to glioma genesis and how this may be associated with changes in cadherin expression is discussed.