All possess a protein/protein interaction motif (BTB/POZ) at the N-terminus that allows protein homo and multimerization and one or several zinc-finger DNA-binding motifs ( Bonchuk et al., 2011). They include Drosophila Broad-complex factors (BR-C), Bric-à-brac (Bab), and several pox virus zinc-finger proteins ( Chaharbakhshi and Jemc, 2016). Disentangling the molecular mechanisms that control the balance between proliferation and differentiation is essential for understanding the formation and maintenance of organisms, as well as human diseases, such as cancer, in which this process is disturbed.īTB-ZF transcription factors are involved in a wide variety of biological processes ( Kelly and Daniel, 2006). The transit from a proliferative to cell-cycle arrested state during this process is tightly regulated and requires changes in transcriptional programs. Division of precursor cells gives rise to daughter cells that differentiate and acquire specific fates. Such cell diversity is generated from a restricted set of precursor cells producing a limited number of differentiated cells.
Organisms are composed of morphologically and functionally distinct cell types. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate commitment. In the Drosophila bristle cell lineage, we show that Ttk69 (1) promotes cell-cycle exit by downregulating the expression of cycE, the cyclin involved in S-phase entry, and (2) regulates terminal cell fate acquisition by downregulating that of hamlet and upregulating that of Suppressor of Hairless, two transcription factors involved in neural-fate acquisition and accessory-cell differentiation, respectively. Here, we show that Tramtrack-69 (Ttk69, a BTB-ZF transcription factor ortholog of the human PLZF factor) plays an essential role in controlling the balance between cell proliferation and cell fate determination. The equilibrium between cell divisions that maintains stem cell fates and terminal cell divisions in which daughter cells adopt post-mitotic fates is essential to assure the correct number of determined cells at a given time at a given place.
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