Piccolo NuA4-Catalyzed Acetylation of Nucleosomal Histones: Critical Roles of an Esa1 Tudor/Chromo Barrel Loop and an Epl1 Enhancer of Polycomb A (EPcA) Basic Region

Center for Gene Regulation, Department of Biochemistry & Molecular Biology, 108 Althouse Laboratory, The Pennsylvania State University, University Park, PA 16802-1014.
Molecular and Cellular Biology (Impact Factor: 4.78). 10/2012; 33(1). DOI: 10.1128/MCB.01131-12
Source: PubMed


Piccolo NuA4 is an essential yeast histone acetyltransferase (HAT) complex that targets histones H4 and H2A in nucleosome
substrates. While Piccolo NuA4's catalytic subunit Esa1 alone is unable to acetylate nucleosomal histones, its accessory subunits,
Yng2 and Epl1, enable Esa1 to bind to and to act on nucleosomes. We previously determined that the Tudor domain of Esa1 and
the EPcA homology domain of Epl1 play critical roles in Piccolo NuA4's ability to act on the nucleosome. In this work, we
pinpoint a loop within the Esa1 Tudor domain and a short basic region at the N terminus of the Epl1 EPcA domain as necessary
for this nucleosomal HAT activity. We also show that this Esa1 Tudor domain loop region is positioned close to nucleosomal
DNA and that the Epl1 EPcA basic region is in proximity to the N-terminal histone H2A tail, the globular region of histone
H4, and also to nucleosomal DNA when Piccolo NuA4 interacts with the nucleosome. Since neither region identified is required
for Piccolo NuA4 to bind to nucleosomes and yet both are needed to acetylate nucleosomes, these regions may function after
the enzyme binds nucleosomes to disengage substrate histone tails from nucleosomal DNA.

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    • "The small region mapped on JADE and BRPF proteins is related to a similar N-terminal region of the EPC1/Epl1 scaffold subunits of the TIP60 (humans) and NuA4 (yeast) H4/H2A-specific HAT complexes . It previously had been shown to be important for binding to nucleosomes and for acetylation and was found to interact with the histone H2A N-terminal tail within the nucleosome (Selleck et al. 2005; Chittuluru et al. 2011; Huang and Tan 2013). Further analysis demonstrated that this domain was essential for Tip60/NuA4 to acetylate the nucleosomal H4 tail, while acetylation of the nucleosomal H2A tail was still detected (Lalonde et al. 2013). "
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