Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development

Abstract

<jats:p>The DNA and protein complex known as chromatin is subject to post-translational modifications (PTMs), which regulate cellular functions, such that PTM dysregulation can lead to disease including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyl transferase (HAT) family of proteins perform histone acetylation. In humans, MOF (hMOF), a member of the MYST family of HATs, acetylate histone H4 at lysine 16 (H4K16ac). MOF-mediated acetylation plays a critical roles in the DNA damage response (DDR) and embryonic stem cell development. Functionally, MOF is found in two distinct complexes NSL in humans (Non Specific Lethal) and MSL (Male Specific Lethal) in flies. NSL complex is also being able to acetylate additional histone H4 sites. Dysregulation of MOF activity occurs in multiple cancers including ovarian, medulloblastoma, breast, colorectal and lung cancer. Bioinformatics analysis of <jats:italic>KAT8</jats:italic>, the gene encoding hMOF, indicated it is highly overexpressed in kidney tumors as part of a concerted gene co-expression program that would support high levels of chromosome segregation and cell proliferation. The linkage between MOF and tumor proliferation suggests there are additional functions of MOF that remain to be discovered.</jats:p>

The Roles of DNA Demethylases in Triple-Negative Breast Cancer

“…These different modifications and the expression levels of the modifying enzymes can influence the open and closed states of the chromatin that lead to changes in gene expression. Many aberrations in these modifications, including both increases or depletions in these marks and their respective modifying enzymes, have been found in breast cancer and are associated with breast cancer initiation, progression, and prognosis [ 15 , 16 , 17 , 18 , 19 , 20 ]. Non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are untranslated RNA molecules that can also influence gene expression and their expression can also be regulated by epigenetic mechanisms.…”

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis

“…Histone acetylation is acknowledged as a kind of biological process. Histone acetylation is mediated by two kinds of enzymes: histone acetyl transferases (HATs) and histone deacetylases (HDACs) [ 7 ]. The histone deacetylase (HDAC) family of transcriptional corepressors, which have been central in the understanding, have emerged as important regulators of cancer biogenesis.…”

p300/Sp1-Mediated High Expression of p16 Promotes Endothelial Progenitor Cell Senescence Leading to the Occurrence of Chronic Obstructive Pulmonary Disease

“…Activated HAT enables p300/CBP the ability to affect chromatin activity through nucleosome histone modification. Current available data reveal that Sp1 and p300 perform cooperative work in the transcriptional regulation of several genes [30,31]. Sp1, as a critical transcription factor in mammals, is closely associated with the formation of the Sp1/HAT complex [32,33].…”