Histone acetyltransferase complexes: one size doesn't fit all

Abstract

Over the past 10 years, the study of histone acetyltransferases (HATs) has advanced significantly, and a number of HATs have been isolated from various organisms. It emerged that HATs are highly diverse and generally contain multiple subunits. The functions of the catalytic subunit depend largely on the context of the other subunits in the complex. We are just beginning to understand the specialized roles of HAT complexes in chromosome decondensation, DNA-damage repair and the modification of non-histone substrates, as well as their role in the broader epigenetic landscape, including the role of protein domains within HAT complexes and the dynamic interplay between HAT complexes and existing histone modifications.

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

“…Mammalian GCN5/PCAF and p300/CBP are two pairs of HATs well known to have important roles in diverse cellular processes (reviewed in Goodman and Smolik, 2000;Sterner and Berger, 2000;Roth et al, 2001;Lee and Workman, 2007). MOZ and MORF constitute a third pair (Figure 1).…”

“…Like HAT1, Gcn5, PCAF and many other HATs Lee and Workman, 2007;Nagy and Tora, 2007;Parthun, 2007), MOZ and MORF are catalytic components of protein complexes. They were recently found to be stoichiometric subunits of ING5 (inhibitor of growth 5) complexes (Doyon et al, 2006).…”

“…Within this program, histone acetyltransferases (HATs) play an integral role (reviewed in Sterner and Berger, 2000;Roth et al, 2001;Yang, 2004;Lee and Workman, 2007). As a pair of such enzymes, MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor) are important for different developmental programs and have been implicated in leukemogenic and other tumorigenic processes.…”

Epigenetic regulation of aging stem cells

“…HATs are diverse in their structures and substrates and are often multisubunit complexes (Lee and Workman, 2007). HDACs can be divided into several classes based on sequence homology and cofactor dependency: class I, II and IV HDACs are classical HDACs requiring Zn 2 þ as a cofactor, whereas class III HDACs, also known as Sirtuins, require NAD þ as a cofactor (Imai et al, 2000;Haigis and Guarente, 2006;Yang and Seto, 2007).…”

Nutrition, Histone Epigenetic Marks, and Disease

“…Acetylation of histones is catalyzed by histone acetyl transferases (HATs) such as PCAF, STAGA, and TFTC, which are grouped on the basis of their catalytic domains such as GCN5 and PCAF {see (Lee and Workman 2007) for an excellent review}. Little is known about dietary modulation of HAT activity; however, the dietary polyphenol curcumin is an inhibitor of the acetyl transferase p300 (Morimoto et al 2008).…”