The MYST family of histone acetyltransferases and their intimate links to cancer

Abstract

The histone acetyltransferases (HATs) of the MYST family are highly conserved in eukaryotes and carry out a significant proportion of all nuclear acetylation. These enzymes function exclusively in multisubunit protein complexes whose composition is also evolutionarily conserved. MYST HATs are involved in a number of key nuclear processes and play critical roles in genespecific transcription regulation, DNA damage response and repair, as well as DNA replication. This suggests that anomalous activity of these HATs or their associated complexes can easily lead to severe cellular malfunction, resulting in cell death or uncontrolled growth and malignancy. Indeed, the MYST family HATs have been implicated in several forms of human cancer. This review summarizes the current understanding of these enzymes and their normal function, as well as their established and putative links to oncogenesis.

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

“…In addition, biochemical analysis has indicated that ING4 interacts with methylated histone H3 (12)(13)(14) and with the HB01-JADE-hEAF6 histone acetyltransferase complex (11). This latter complex is responsible for most nucleosomal histone H4 acetylation in eukaryotes, and knockdown experiments indicated that Ing4-HB01 association is required for cells to progress properly through the DNA synthesis (S) phase of the cell cycle (15,16).…”

HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention

“…Esa1 and TIP60 are orthologous and belong to the MYST family (Doyon and Cote, 2004). Compared to Gcn5/PCAF and p300/CBP, this family is less well known, so it is extensively covered in this edition, Lafon et al (2007) on Esa1, Sas2 and Sas3, the three MYST proteins from yeast; Rea et al (2007) covering mammalian orthologs of Mof (male absent on the first), a key regulator of Drosophila gene dosage compensation; Avvakumov and Coˆte´(2007) outlining the characterization of mammalian MYST proteins; and Yang and Ullah (2007) detailing studies of MOZ and MORF (MOZ-related factor), a pair of paralogs with direct links to leukemia and highly conserved from zebrafish to mammals. In addition to those mentioned above, over 10 other proteins have been reported to possess HAT activity (for reviews, see Sterner and Berger, 2000;Roth et al, 2001;Yang, 2004;Lee and Workman, 2007).…”

Subunit Composition and Substrate Specificity of a MOF-containing Histone Acetyltransferase Distinct from the Male-specific Lethal (MSL) Complex

“…Based on the nature of their catalytic domains, HATs can be grouped into two distinct families: the GCN5-related N-acetyltransferase (GNAT) family, which includes GCN5 and p300/CBP-associating factor (8), and the Moz-Ybf2/Sas3-Sas2-Tip60 (MYST) family, which is characterized by a highly conserved MYST domain composed of an acetyl-CoA binding motif and a zinc finger (9,10). Some MYST family members also have additional structural features such as chromodomains (MOF, Esa1, and Tip60), plant homeodomain-linked zinc fingers (Moz and MORF), and other domains that bind specifically to modified histones or participate in other protein-protein interactions (10).…”