The Yeast NuA4 and Drosophila MSL Complexes Contain Homologous Subunits Important for Transcription Regulation
ABSTRACT In Drosophila, the MSL complex is required for the dosage compensation of X-linked genes in males and contains a histone acetyltransferase, MOF. A point mutation in the MOF acetyl-CoA-binding site results in male-specific lethality. Yeast Esa1p, a MOF homolog, is essential for cell cycle progression and is the catalytic subunit of the NuA4 acetyltransferase complex. Here we report that NuA4 purified from yeast with a point mutation in the acetyl-CoA-binding domain of Esa1p exhibits a strong decrease in histone acetyltransferase activity, yet has no effect on growth. We demonstrate that Eaf3p (Esa1p-associated factor-3 protein), a yeast protein homologous to the Drosophila dosage compensation protein MSL3, is also a stable component of the NuA4 complex. Unlike other subunits of the complex, it is not essential, and the deletion mutant has no growth phenotype. NuA4 purified from the mutant strain has a decreased apparent molecular mass, but retains wild-type levels of histone H4 acetyltransferase activity. The EAF3 deletion and the ESA1 mutation lead to a decrease in PHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4 expressions. These results, together with those previously obtained with both the MSL and NuA4 complexes, underscore the importance of targeted histone H4 acetylation for the gene-specific activation of transcription.
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- "Recently, a new member of the Sin3 complex, Morf4-Related Gene 15 (MRG15) has been identified which belongs to the MRG family of proteins (Jelinic et al., 2011). MRG15 is known to interact with a number of proteins including tumor suppressor Rb, HDAC1/2, RBP2 and NuA4-KAT5 (Carrozza et al., 2005; Eisen et al., 2001; Hayakawa et al., 2007; Pardo et al., 2002). In yeast, MRG15 interacts with the Sin3-Rpd3 (HDAC) complex in a manner similar to the Inhibitor of Growth (ING) family of proteins implicated in senescence (Han et al., 2006). "
ABSTRACT: Sin3, a large acidic protein, shares structural similarity with the helix-loop-helix dimerization domain of proteins of the Myc family of transcription factors. Sin3/HDAC corepressor complex functions in transcriptional regulation of several genes and is therefore implicated in the regulation of key biological processes. Knockdown studies have confirmed the role of Sin3 in cellular proliferation, differentiation, apoptosis and cell cycle regulation, emphasizing Sin3 as an essential regulator of critical cellular events in normal and pathological processes. The present review covers the diverse functions of this master transcriptional regulator as well as illustrates the redundant and distinct functions of its two mammalian isoforms.European journal of cell biology 10/2013; 92(8). DOI:10.1016/j.ejcb.2013.09.001 · 3.83 Impact Factor
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- "Esa1 is the catalytic component of the NuA4 and piccolo complexes that acetylate histone H4, H2A, and its variant H2A.Z (Allard et al. 1999; Babiarz et al. 2006; Keogh et al. 2006; Millar et al. 2006). Many of the NuA4 subunits , including Esa1, are essential (Galarneau et al. 2000; Loewith et al. 2000; Eisen et al. 2001), indicating that this complex has critical cellular roles. Esa1 has a role in regulating expression of ribosomal protein genes (Reid et al. 2000). "
ABSTRACT: The acetyltransferase Esa1 is essential in the yeast Saccharomyces cerevisiae and plays a critical role in multiple cellular processes. The most well-defined targets for Esa1 are lysine residues on histones. However, an increasing number of nonhistone proteins have recently been identified as substrates of Esa1. In this study, four genes (LYS20, LEU2, VAP1, and NAB3) were identified in a genetic screen as high-copy suppressors of the conditional temperature-sensitive lethality of an esa1 mutant. When expressed from a high-copy plasmid, each of these suppressors rescued the temperature-sensitivity of an esa1 mutant. Only NAB3 overexpression also rescued the rDNA-silencing defects of an esa1 mutant. Strengthening the connections between NAB3 and ESA1, mutants of nab3 displayed several phenotypes similar to those of esa1 mutants, including increased sensitivity to the topoisomerase I inhibitor camptothecin and defects in rDNA silencing and cell-cycle progression. In addition, nuclear localization of Nab3 was altered in the esa1 mutant. Finally, posttranslational acetylation of Nab3 was detected in vivo and found to be influenced by ESA1.G3-Genes Genomes Genetics 10/2012; 2(10):1223-32. DOI:10.1534/g3.112.003558 · 3.20 Impact Factor
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- "However, although homologous to the Set1 component of the Set1/COMPASS complex, studies in C. elegans suggest that MES-4 acts primarily as an autosome-specific H3K36 methyltransferase (Furuhashi et al. 2010; Rechtsteiner et al. 2010). MRG-1 is a member of the NuA4 complex, which promotes acetylation of histone H4 and subsequent exchange with the Htz histone variant (Eisen et al. 2001; Takasaki et al. 2007). The remaining three synMuv suppressor genes and their orthologs in other systems are more poorly characterized at a functional level; proteins encoded by hecd-1, sin-3, and zfp-1 are homolgous to the yeast Ufd4 ubiquitin ligase (Xie and Varshavsky 2000), the Sin3 histone deacetylase (Bernstein et al. 2000; Figure 3 Analysis of suppression by mitochondrial prohibitins. "
ABSTRACT: The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene.Genetics 04/2012; 191(4):1367-80. DOI:10.1534/genetics.112.140152 · 5.96 Impact Factor