The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

Abstract

Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation

“…H4 K16 is acetylated by MOF, which is stably associated with two complexes: NSL-MOF and the MSL1/2-containing MSL-MOF [77]. Of particular interest is the role that MOF-mediated H4 K16ac may play in the formation of heterochromatin.…”

Histone acetyltransferase KAT8 is essential for mouse oocyte development by regulating ROS levels

“…K (lysine) acetyltransferase 8 (KAT8, also known as MOF or MYST1) is a highly conserved MYST family member specifically responsible for H4K16 acetylation (Gupta et al, 2013). KAT8 contains a chromodomain for DNA binding and a C-terminal HAT domain for histone acetylation (Su et al, 2016). It is expressed in most tissues, including the ovary (Thomas et al, 2007), and affects gene expression in multiple biological processes.…”

KATapulting toward Pluripotency and Cancer

“…Mof ( m ales absent o n the f irst) was originally identified in Drosophlia as a regulator of dosage compensation, leading to H4K16ac and hyperactivation of the single male X chromosome 147 . However, it is still unclear whether Mof manages similar dosage compensation effects in mammals.…”