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.
Highlights
The nucleosome as the basic repeating unit of chromatin is composed of chromosomal DNA and a histone octamer, which contains two copies each of the core histones H2A, H2B, H3 and H4
We focus on the Males absent on the first (MOF) and its corresponding histone acetylation, summarize the current understanding of MOF functions on tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways
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Summary
The nucleosome as the basic repeating unit of chromatin is composed of chromosomal DNA and a histone octamer, which contains two copies each of the core histones H2A, H2B, H3 and H4. Loosened chromatin structures will alter their shape, freeing DNA, allowing the binding of transcription factors and other sequence-specific regulators [2]. These changes in chromatin structure regulate many critical DNA transactions, including transcription, replication, recombination and repair. The various modifications of histone N-terminal tails, such as acetylation, methylation, ubiquitination and phosphorylation, via heritably regulating the gene expression, are involved in most cellular biological processes. Current evidence has indicated that disproportionate global histone modifications in cells may play a key role in initiating events in some forms of cancer by altering gene expressions, including aberrant regulation of oncogenes and/or tumor suppressors [7,8]. We focus on the MOF and its corresponding histone acetylation, summarize the current understanding of MOF functions on tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways
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