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

• Type of Material: Article
• Authors: Arri Eisen, Emory University; Rhea T. Utley, Laval University; Amine Nourani, Laval University; Stephane Allard, Laval University; Peter Schmidt, Emory University; William S. Lane, Harvard University; John C. Lucchesi, Emory University; Jacques Cote, Laval University
• Language: English
• Date: 2001-02
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2001 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1074/jbc.M008159200
• Title of Journal or Parent Work: Genes: Structure and Regulation
• Volume: 276
• Issue: 5
• Start Page: 3484
• End Page: 3491
• Grant/Funding Information: This work was supported in part by grants from the Medical Research Council of Canada (to J. C.) and the National Institutes of Health (to J. C. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
• Keywords: Eaf3p; MORF-related gene on chromosome15; actin-relatedprotein-4protein; chromodomain-containing region; high pressure liquid chromatography; Tra1p; male-specific lethal; Eaf3/MSL3/MRG15; polyacrylamide gel electrophoresis; Ada acetyltransferase; NuA4; glutathioneS-transferase; essential Sas2-relatedacetyltransferase-1protein; nucleosome acetyltransferase of histone H4; mortality factor on chromosome 4; enhancer ofPolycomb-like-1protein; histone acetyltransferase; MOZ/YBF2/SAS2/Tip60; altered polarity mutant-13; Spt-Ada-Gcn5acetyltransferase
• Research Categories: Biology, Genetics; Chemistry, Biochemistry

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-associatedfactor-3protein), 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 inPHO5 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.