Exploring the Histone Acetylation Cycle in the Protozoan Model Tetrahymena thermophila

Abstract

The eukaryotic histone acetylation cycle is composed of three classes of proteins, histone acetyltransferases (HATs) that add acetyl groups to lysine amino acids, bromodomain (BRD) containing proteins that are one of the most characterized of several protein domains that recognize acetyl-lysine (Kac) and effect downstream function, and histone deacetylases (HDACs) that catalyze the reverse reaction. Dysfunction of selected proteins of these three classes is associated with human disease such as cancer. Additionally, the HATs, BRDs, and HDACs of fungi and parasitic protozoa present potential drug targets. Despite their importance, the function and mechanisms of HATs, BRDs, and HDACs and how they relate to chromatin remodeling (CR) remain incompletely understood. Tetrahymena thermophila (Tt) provides a highly tractable single-celled free-living protozoan model for studying histone acetylation, featuring a massively acetylated somatic genome, a property that was exploited in the identification of the first nuclear/type A HAT Gcn5 in the 1990s. Since then, Tetrahymena remains an under-explored model for the molecular analysis of HATs, BRDs, and HDACs. Studies of HATs, BRDs, and HDACs in Tetrahymena have the potential to reveal the function of HATs and BRDs relevant to both fundamental eukaryotic biology and to the study of disease mechanisms in parasitic protozoa.

Exploration of the Nuclear Proteomes in the Ciliate Oxytricha trifallax

“…Indeed, homologs of the H3/H4 histone acetyltransferases Gcn5, Hat1, and NuA4, are readily identified in the Oxytricha MAC genome ( Supplemental Table S5 ), and one of these Gcn5 homologs is present in our nuclear mass spectrometry dataset. These enzymes are conserved across eukaryotes, including Tetrahymena , yeast, plants, and animals [ 42 ]. They are likely to be responsible for the extensive H3 and H4 histone acetylation observed in Oxytricha MAC histones.…”

HAP2-Mediated Gamete Fusion: Lessons From the World of Unicellular Eukaryotes

“…Aside from work on HAP2/GCS1 and fertilization more generally, Tetrahymena has served as a key model for the study of genome editing (Cheng et al, 2019); stimulusdependent secretion (Turkewitz, 2004); ciliary and microtubule-based motility (Gibbons and Rowe, 1965;Vale and Yano Toyoshima, 1988;Suryavanshi et al, 2010;Reynolds et al, 2018); ribosome structure and function (Rabl et al, 2011;Wilson and Doudna Cate, 2012); transgenerational inheritance and the role of small RNAs in chromatin dynamics (Couzin, 2002;Liu et al, 2007;Noto and Mochizuki, 2017;Neeb and Nowacki, 2018;Bastiaanssen and Joo, 2021). Tetrahymena has also been responsible for major discoveries in the areas of telomere structure and biosynthesis (Blackburn et al, 2006;Jiang et al, 2015); catalytic (self-splicing) RNAs (Herschlag and Cech, 1990;Hedberg and Johansen, 2013); and the role of histone modifications in gene expression (Brownell et al, 1996;Allis and Jenuwein, 2016;Wahab et al, 2020).…”

Histone Chaperone Nrp1 Mutation Affects the Acetylation of H3K56 in Tetrahymena thermophila

“…H3K56 acetylation appears to be widely distributed throughout polytene chromosomes in Drosophila [35]. H3K56 acetylation occurs extensively in MAC of Tetrahymena [36]. Asf1 and Rtt109 are required for global H3K56 acetylation in Schizosaccharomyces pombe [37].…”