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

ABSTRACT: Three Saccharomyces cerevisiae proteins (Yng1/YOR064c, Yng2/YHR090c, and Pho23) and two Schizosaccharomyces pombe proteins (Png1/CAA15917 and Png2/CAA21250) share significant sequence identity with the human candidate tumor suppressor p33(ING1) in their C-terminal regions. The homologous regions contain PHD finger domains which have been implicated in chromatin-mediated transcriptional regulation. We show that GFP-Yng2, like human Ing1, is localized in the nucleus. Deletion of YNG2 results in several phenotypes, including an abnormal multibudded morphology, an inability to utilize nonfermentable 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, 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 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.

SUBMITTER: Loewith R

PROVIDER: S-EPMC85704 | biostudies-literature | 2000 Jun

REPOSITORIES: biostudies-literature

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

Loewith R R Meijer M M Lees-Miller S P SP Riabowol K K Young D D

Molecular and cellular biology 20000601 11

Three Saccharomyces cerevisiae proteins (Yng1/YOR064c, Yng2/YHR090c, and Pho23) and two Schizosaccharomyces pombe proteins (Png1/CAA15917 and Png2/CAA21250) share significant sequence identity with the human candidate tumor suppressor p33(ING1) in their C-terminal regions. The homologous regions contain PHD finger domains which have been implicated in chromatin-mediated transcriptional regulation. We show that GFP-Yng2, like human Ing1, is localized in the nucleus. Deletion of YNG2 results in se ...[more]

PMID: 10805724

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Project description:ESA1 (essential SAS-family acetyltransferase) is the only known yeast histone acetyltransferase (HAT) required for cell viability. It is a member of the MYST (MOZ, YBF2/SAS3, SAS2, Tip60) family of HAT proteins and contains a conserved acetyltransferase domain in addition to a chromodomain. While ESA1’s HAT activity is important in processes such as deoxyribonucleic acid (DNA) repair, acetylation is likely not its essential function. Our lab has shown that mutants with a single point mutation in the active site cysteine are still viable even though their acetyltransferase abilities are abolished. Furthermore, chromatin immunoprecipitation assays have shown ESA1 distributed evenly along the length of chromatin, not localized to specific promoters as would be expected from a HAT protein involved in transcriptional regulation. As is the case for other HAT proteins, ESA1’s acetyltransferase activity is significant, but in processes such as DNA replication, DNA repair and cell cycle progression. The aim of this project is to determine the essential function of ESA1 - the catalytic subunit of the yeast HAT complex, NuA4 (nucleosome acetyltransferase of H4) – using a bypass suppression screen to identify suppressors of ESA1. It is proposed that suppressing mutations will alter a gene involved in the process that is the essential function of ESA1. Thus, identifying a suppressor that can bypass the need for ESA1 may provide insight into its essential function. Since ESA1 is an essential gene, a haploid esa1∆ strain in which wild-type ESA1 is provided on a centromeric plasmid was utilized. The bypass suppression screen resulted in suppressors of ESA1 that allowed esa1∆ cells to be viable even in the absence of the essential gene. These second site suppressors (sup-) of ESA1 each show the Mendelian segregation pattern of the suppressing gene and ESA1 in 2:2 ratios, implying they are single genes unlinked to ESA1. Microarray and nuclear morphology studies show abnormal gene expression and morphology of the esa1- sup- cells, further implicating the suppressing mutation in DNA repair and replication processes. Investigating ESA1’s essential role and a probable conservation of function across species can provide a deeper understanding of the capabilities of HAT complexes. Keywords: Comparison of strains lacking essential ESA1 gene to those containing an ESA1 bypass suppressor.

Dataset Information

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

Publications

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

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