Getting a Transcription Factor to Only One Nucleus Following Mitosis

Primer T he growth and development of all eukaryotes depends on the process of asymmetric cell division, in which a single cell gives rise to two genetically identical cells that adopt distinct fates [1,2]. Asymmetry occurs when two cells are exposed to different environmental stimuli or when specific mRNAs or proteins (known as cell fate determinants) are segregated unequally. In recent years, studies in a variety of organisms have furthered our understanding of how these factors can cause two cells from the same division to experience different transcriptional outcomes, and thus take different paths. One model system for the study of asymmetric gene expression is the budding yeast Saccharomyces cerevisiae. Asymmetry in S. cerevisiae is defined as the difference between a " mother " yeast cell and the smaller " daughter " cell that forms by budding from the original mother cell. One well-characterized example of this asymmetry is the mother cell–specific expression of the HO endonuclease gene that causes mother cells to switch mating type, a programmed genetic recombination that changes this dimorphic organism from one sex to the other [3]. HO is not expressed in daughter cells because the Ash1 transcriptional repressor is present in much higher amounts in daughter than in mother cells. The ASH1 gene is transcribed during early M phase in both mother and daughter cells, but the ASH1 mRNA is transported to the distal tip of the daughter cell during mitosis at a time when the cytoplasms of the two cells are still connected. The mRNA is then translated in the daughter cell, and the Ash1 protein binds to the HO promoter and represses its transcription. A second example of asymmetric segregation of proteins in yeast is the daughter-specific nuclear localization of the Ace2 transcriptional activator [4]. Ace2 directs expression of daughter-specific genes involved in separation of mother and daughter cells following mitosis. In this case, the Ace2 protein is transcribed and translated in both mother and daughter cells, but accumulates specifically in the daughter cell nucleus. Studies have demonstrated that the mechanisms controlling asymmetric localization of Ash1 and Ace2 are distinct and require different sets of protein factors. A new study in PLoS Biology by Mazanka et al. [5] sheds light on the factors involved in regulating this unequal segregation with a detailed look at the mechanism underlying Ace2 asymmetry. The Ace2 transcription factor shares many similarities with a homologous zinc finger DNA-binding …