Disease relevance of ESA1

• Esa1 is the catalytic subunit of the NuA4 histone acetylase (HAT) complex that acetylates histone H4, and it is a member of the MYST family of HAT proteins that includes the MOZ oncoprotein and the HIV-1 Tat interacting protein Tip60 [1].

High impact information on ESA1

• The purified Esa1-Arp4 HAT complex acetylates linear nucleosomal arrays with far greater efficiency than circular arrays in vitro, indicating that it preferentially acetylates nucleosomes near a break site [2].
• Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair [2].
• The data presented here demonstrate that while Htz1 is associated preferentially with the promoters of repressed genes, K14 acetylation is enriched at the promoters of active genes, and requires two known histone acetyltransferases, Gcn5 and Esa1 [3].
• The picNuA4 complex contains Esa1, Epl1, and Yng2 as subunits and strongly prefers chromatin over free histones as substrate [4].
• These results indicate that the essential aspect of Esa1 and Epl1 resides in picNuA4 function [4].

Biological context of ESA1

• For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death [5].
• Our findings do reveal that of these HATs, only Gcn5 and Esa1 contribute substantially to gene expression genome wide [6].
• 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 [7].
• Strains carrying these mutations are also blocked in the cell cycle such that at restrictive temperatures, esa1 mutants succeed in replicating their DNA but fail to proceed normally through mitosis and cytokinesis [8].
• We find that the conserved Enhancer of Polycomb A (EPcA) homology region of the Epl1 component and the N-terminal 165 amino acids of the Yng2 component of Piccolo are sufficient with Esa1 to specifically act on nucleosomes [9].

Anatomical context of ESA1

• Although Esa1, the catalytic subunit of NuA4, is essential for viability, we found that yaf9 Delta mutants are viable but hypersensitive to microtubule depolymerizing agents and synthetically lethal with two different mutants of the mitotic apparatus [10].
• Full-length recombinant EhMYST protein demonstrated HAT activity with calf thymus histones and showed a preference for histone H4, similar to the yeast MYST protein, Esa1 [11].

Associations of ESA1 with chemical compounds

• Yeast ESA1 is a member of the MYST subfamily of histone acetyltransferases (HATs), which use acetyl-coenzyme A (CoA) to acetylate specific Lys residues within histones to regulate gene expression [12].

Physical interactions of ESA1

• In living cells, Swc4p is present in a megadalton protein complex that shows a fractionation behavior in gel filtration similar to that of Esa1p, the histone acetyltransferase of the NuA4 complex [13].

Other interactions of ESA1

• Genetic and biochemical evidence indicate that the Yng2-associated HAT is Esa1, suggesting that Yng2 is a component of the NuA4 HAT complex [14].
• Gcn5p is recruited to SUC2 simultaneously with SWI/SNF, whereas Esa1p associates constitutively with the promoter [15].
• Using Chromatin IP analysis, we found that Esa1-dependent histone H4 acetylation at the PHO5 promoter correlates with specific recruitment of the NuA4 complex to this locus under repressing conditions [16].
• O5257 shows homology with the SAS2 protein and another hypothetical protein from yeast [17].
• Esa1p and Gcn5p counteract URA3 silencing even when they are targeted 1.7 kb downstream of the promoter and >2.0 kb from the silencer [18].

Analytical, diagnostic and therapeutic context of ESA1

• To address what features of chromatin modification complexes are responsible for the specific recognition of nucleosomes compared to naked histones, we have performed a functional dissection of the Esa1-containing Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex [9].

References