Males absent on the first (MOF): from flies to humans

Abstract

Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible for acetylating histone H4 at lysine 16 (H4K16) and is a key component of the MSL complex required for dosage compensation in Drosophila. The human ortholog of MOF (hMOF) has the same substrate specificity and recent purification of the human and Drosophila MOF complexes showed that these complexes were also highly conserved through evolution. Several studies have shown that loss of hMOF in mammalian cells leads to a number of different phenotypes; a G 2 /M cell cycle arrest, nuclear morphological defects, spontaneous chromosomal aberrations, reduced transcription of certain genes and an impaired DNA repair response upon ionizing irradiation. Moreover, hMOF is involved in ATM activation in response to DNA damage and acetylation of p53 by hMOF influences the cell's decision to undergo apoptosis instead of a cell cycle arrest. These data, highlighting hMOF as an important component of many cellular processes, as well as links between hMOF and cancer will be discussed.

Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPα

“…This family of HATs has been linked to mediate long-lasting epigenetic changes of chromatin (for example, mof in Drosophila is responsible for X chromosome dosage compensation 21 ). Additionally, the acetyl transferase activity of TIP60 on nucleosomal histones in the presence of other factors has been reported, and TIP60 can function both as a transcriptional co-activator or as a co-repressor, connecting a number of different factors to the basal transcriptional machinery.…”

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

“…Finally, K16 acetylation is important in epigenetic regulation as substantiated by its being the only lysine residue among the N-terminal tails of all histones that is targeted by an exclusive category of HATs, such as some members of the MYST family (Sterner and Berger, 2000;Rea et al, 2007), as well as some HDACs, like the Sir2 family, known as the Sirtuins in higher eukaryotes (see below).…”

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

“…Metazoan TIP60 proteins are orthologous to Esa1 owing to similar domain organization, complex formation and cellular function . At the functional level, metazoan MOF proteins are somewhat similar to Sas2 (Rea et al, 2007). Like TIP60 and MOF, human HBO1 is highly homologous to its counterpart in Drosophila (Hilfiker et al, 1997;Iizuka and Stillman, 1999;Smith et al, 2005;Mendjan et al, 2006).…”

“…It is now known that MYST proteins have important roles in various biological processes (Ceol and Horvitz, 2004;Kusch et al, 2004;Dou et al, 2005;Smith et al, 2005;Mendjan et al, 2006;Sykes et al, 2006;Tang et al, 2006). These enzymes have been the subjects of several excellent reviews Squatrito et al, 2006;Avvakumov and Coˆte´, 2007;Lafon et al, 2007;Rea et al, 2007;Thomas and Voss, 2007). MOZ and MORF are quite different from other members of this family (Figure 1), so we devote the following sections to this pair of HATs.…”