Controlling Epithelial to Mesenchymal Transition through Acetylation of Histone H2BK5

Abstract

Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT. For example, in trophoblast stem (TS) cells, H2BK5Ac promotes the expression of genes important to the maintenance of an epithelial phenotype. This finding led to the discovery that TS cells and stem-like claudin-low breast cancer cells share similar H2BK5Ac-regulated gene expression, linking developmental and cancer cell EMT. An improved understanding of the role of H2BK5Ac in developmental EMT and stemness will further our understanding of epigenetics in EMT-related pathologies. Here, we examine the binders and regulators of H2BK5Ac and discuss the roles of H2BK5Ac in stemness and EMT.

Keywords: CBP; EMT; H2BK5 acetylation; HDAC6; MAP3K4.

Figure 1. Interactors and Regulators of H2BK5Ac

Figure 2. Modifiers of H2BK5Ac control the expression of epithelial genes in TS cells