Mobley Robert J, Abell Amy N
Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA.
J Nat Sci. 2017 Sep;3(9).
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.
当具有细胞间黏附和顶-基极性的上皮细胞通过一种称为上皮-间质转化（EMT）的过程转变为侵袭性的、单个的间充质细胞时，会发生大规模的表观遗传变化。重要的是，具有干细胞特性的癌症会通过重新激活发育性EMT程序而扩散并形成远处转移。最近的研究表明，表观遗传组蛋白修饰H2BK5乙酰化（H2BK5Ac）在EMT的调控中很重要。例如，在滋养层干细胞（TS）中，H2BK5Ac促进对维持上皮表型至关重要的基因的表达。这一发现导致了TS细胞和干细胞样紧密连接蛋白低表达的乳腺癌细胞具有相似的H2BK5Ac调控基因表达的发现，将发育和癌细胞EMT联系起来。对H2BK5Ac在发育性EMT和干性中的作用有更深入的了解，将有助于我们进一步理解EMT相关病理中的表观遗传学。在这里，我们研究了H2BK5Ac的结合蛋白和调节因子，并讨论了H2BK5Ac在干性和EMT中的作用。
