Three yeast proteins related to the human candidate tumor suppressor p33(ING1) are associated with histone acetyltransferase activities

Three Saccharomyces cerevisiae proteins (Yng1/YOR064c, Yng2/YHR090c, and Ph o23) and two Schizosaccharomyces pombe proteins (Png1/CAA15917 and Png2/CAA 21250) share significant sequence identity with the human candidate tumor s uppressor p33(ING1) in their C-terminal regions. The homologous regions con tain PHD finger domains which have been implicated in chromatin-mediated tr anscriptional regulation. We show that GFP-Yng2, like human Ing1, is locali zed in the nucleus. Deletion of YNG2 results in several phenotypes, includi ng an abnormal multibudded morphology, an inability to utilize nonfermentab le carbon sources, heat shock sensitivity, slow growth, temperature sensiti vity, and sensitivity to caffeine. These phenotypes are suppressed by expre ssion of either human Ing1 or S. pombe Png1, suggesting that the yeast and human proteins are functionally conserved. Yng1- and Pho23-deficient cells also share some of these phenotypes. We demonstrated by yeast two-hybrid an d coimmunoprecipitation tests that Yng2 interacts with Tra1, a component of histone acetyltransferase (HAT) complexes. We further demonstrated by coim munoprecipitation that HA-Yng1, HA-Yng2, HA-Pho23, and HA-Ing1 are associat ed with HAT activities in yeast. Genetic and biochemical evidence indicate that the Yng2-associated HAT is Esa1, suggesting that Yng2 is a component o f the NuA4 HAT complex. These studies suggest that the yeast Ing1-related p roteins are involved in chromatin remodeling. They further suggest that the se functions may be conserved in mammals and provide a possible mechanism f or the human Ing1 candidate tumor suppressor.