The Yeast NuA4 and Drosophila MSL Complexes Contain Homologous Subunits Important for Transcription Regulation

Laval University, Quebec City, Quebec, Canada
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2001; 276(5):3484-91. DOI: 10.1074/jbc.M008159200
Source: PubMed


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-associatedfactor-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 EAF3deletion and the ESA1 mutation lead to a decrease inPHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4expressions. 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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    • "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). "
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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. "
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