The zinc finger protein ZPR1 is present in both the cytoplasm and nucleoplasm. Cell cycle analysis demonstrates that ZPR1 undergoes major changes in subcellular distribution during proliferation. ZPR1 is diffusely localized throughout the cell during the G(1) and G(2)/M phases of the cell cycle. In contrast, ZPR1 redistributes to the nucleus during S phase and ZPR1 exhibits prominent co-localization with the survival motor neurons protein and the histone gene-specific transcription factor NPAT in subnuclear foci, including Cajal bodies that associate with histone gene clusters. ZPR1 deficiency causes disruption of survival motor neurons and NPAT localization within the nucleus, blocks S phase progression, and arrests cells in both the G(1) and G(2) phases of the cell cycle. These changes in subnuclear architecture and cell cycle progression may be caused by transcriptional defects in ZPR1-deficient cells, including decreased histone gene expression.