Modulation of the Zac1's transactivation and coactivation functions via PML and Daxx within distinct subcellular localizations.

Zac1 acts as a transcription factor and a transcriptional cofactor cooperated with histone acetyltransferases and/or histone deacetylases. The molecular mechanisms underlying the subcellular localization and specificity of Zac1 transcriptional regulation are unclear. Here, we show that Zac1 might have physical and functional interactions with death-associated protein (Daxx) and promyelocytic leukemia protein (PML). However, unlike Daxx, nuclear Zac1 was not relocalized into PML nuclear bodies (PML-NBs). The enhancement of the transactivation activity of Zac1 by PML and Daxx might occur outside PML-NBs. Other components of PML-NBs, such as CREB-binding protein (CBP), ubiquitin-conjugating enzyme 9, and p53, were also regulatory targets for Zac1, for whom the locations to mediate its regulatory functions were distinct from PML-NBs. Our findings further suggest that Zac1 might play differential roles over the functions of CBP depending on the status of post-translational modification on CBP. Hence, our results link PML-NB components to the transactivation and coactivation functions of Zac1 at non-PML-NB sites.