Three S. cerevisiae
proteins (Yng1, Yng2, and Pho23) and two S. pombe proteins
(Png1 and Png2) share significant sequence identity with the human
candidate tumor suppressor Ing1 in their C-terminal regions. The
homologous regions contain PHD finger domains which have been
implicated in chromatin-mediated transcriptional regulation. We have
shown that GFP-Yng2, like human Ing1, is localized in the
nucleus. Deletion of YNG2 results in several phenotypes, including an
abnormal multi-budded morphology, an inability to utilize
non-fermentable carbon sources, heat-shock sensitivity, slow growth,
temperature sensitivity, and sensitivity to caffeine. These phenotypes
are suppressed by expression of either human Ing1 or S. pombe
Png1. Yng1 and Pho23 deficient cells also share some of these
phenotypes. We demonstrated by yeast two-hybrid and
coimmunoprecipitation tests that Yng2 interacts with Tra1, a component
of histone acetyltransferase (HAT) complexes. We further demonstrated
by coimmunoprecipitation that HA-Yng1, HA-Yng2, HA-Pho23, and HA-Ing1
are associated with HAT activities in yeast. Genetic and biochemical
evidence indicate that the Yng2-associated HAT is Esa1, suggesting
that Yng2 is a component of the NuA4 HAT complex. These studies
suggest that the yeast Ing1 related proteins are involved in chromatin
remodeling. They further suggest that these functions may be
conserved in mammals, and provide a possible mechanism for the human
Ing1 candidate tumor suppressor.
Return to YGM 2000 Abstract Index