Topoisomerase II (topo II) catalyzes the decatenation of interlinked DNA molecules and is essential for chromosome segregation. To test the hypothesis that the noncatalytic C-terminal domain of topo II is necessary for mediating interactions with other proteins required for chromosome segregation, we used a two-hybrid cloning strategy to identify proteins that interact with S. cerevisiae topo II in vivo. One protein identified (Sgs1p) is structurally related to E. coli RecQ protein and contains helicase signature motifs. Strains lacking Sgs1p exhibit elevated levels of chromosome misseggregation during both mitotic and meiotic division. We propose a model to account for the interaction of a topoisomerase and a helicase in the faithful segregation of newly replicated eukaryotic chromosomes.

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IFN-γ is a potent pleiotropic Th1 cytokine, the production of which is tightly regulated during fetal development. Negative control of fetal/neonatal IFN-γ production is generally attributed to the Th1-antagonistic effect of mediators produced by the placenta, but evidence exists of additional and more direct transcriptional regulation. We report that neonatal (cord blood) CD3+/CD45RO− T cells, in particular the CD4+/CD45RO− subset, are hypermethylated at CpG and non-CpG (CpA and CpT) sites within and adjacent to the IFN-γ promoter. In contrast, CpG methylation patterns in cord blood IFN-γ-producing CD8+/CD45RO− T cells and CD56+/CD16+/CD3− NK cells did not differ significantly from those in their adult counterparts. Consistent with this finding, IFN-γ production by stimulated naive cord blood CD4+ T cells is reduced 5- to 10-fold relative to adult CD4+ T cells, whereas production levels in neonatal and adult CD8+ T cells are of a similar order. Evidence of significant CpA and CpT methylation was not discovered in promoter sequence from other cytokines (IL-4, TNF-α, or IFN-γR α-chain). We additionally demonstrate that overexpression of DNA methyltransferase 3a in embryonic kidney carcinoma cells is accompanied by CpA methylation of the IFN-γ promoter.