Progress on epigenetic regulation of iron homeostasis / 浙江大学学报·医学版

ABSTRACT

Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(), transferrin receptor 1(), transferrin receptor 2(), ferroportin(), hepcidin(), hemojuvelin() and . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of , and bone morphogenetic protein 6 () genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses gene expression. On the contrary, HADC inhibitor upregulates gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.