SET Domain Protein Regulates S. pombe Cytokinesis Figure 10. set3D mutants are impaired in their ability mount a proper transcriptional response to LatA treatment. (A) Volcano plot analysis of the expression of genes annotated by GO as having a cellular response to stress. The response of wild-type cells (left panel) and set3D mutants (right panel) treated with LatA are shown. Horizontal green lines represent a p-value of 0.05. Vertical green lines represent the threshold for a 1.5 fold change in expression. Red squares indicate differentially expressed genes. (B) Scatter plot analysis comparing the expression of stress response genes (both CESR genes and genes annotated by GO as having a cellular response to stress) in response to LatA treatment. Blue squares indicates data points for wild type cells. Red diamonds indicate data points for set3D mutants. Genes up-regulated in response to LatA in wild-type cells are highlighted with a blue oval. Genes down-regulated in response to LatA in wild-type cells are highlighted with a pink oval. doi:10.1371/journal.pone.0031224.g010 interesting to speculate as to whether MLL5, NCOR2, or TBL1X might indeed encode tumour suppressors, and if so, whether the loss of these genes, and any ensuing cytokinesis defects could be relevant to carcinogenesis. Regardless, the isolation of known human regulators of cytokinesis in this screen further supports the utility of using S. pombe as a model for the study of eukaryotic genetic regulatory networks. A second observation of particular significance is the discovery that the levels of Set3p, Hif2p, and Snt1p increase 2–3 fold when wild-type cells are grown in the presence of low doses of LatA (Figure 5). Thus, in addition to the observed LatA hypersensitivity exhibited by the gene deletion mutants, these data provide further independent support that activity of the complex is required to respond properly to the presence of LatA in the growth medium. Up-regulation probably occurs at the post-transcriptional level since microarray data did not show strong induction of these genes in wild-type cells treated with LatA (File S1). While the above data identifies the Set3p complex as being required for the proper response to LatA induced stress, it says little with respect to the mechanism of action. Since histone de- acetylase complexes have well defined roles in transcriptional regulation, we considered the possibility that the observed PLoS ONE | www.plosone.org 12 February 2012 | Volume 7 | Issue 2 | e31224