Epigenetics: Reprogrammable interface of the genome and environments

In the past decade, the genes involved in the pathogenesis of type 1 and type 2 diabetes have been identified by a comprehensive search over the whole genome, the genome-wide association study (GWAS). The method is now carried out by a dramatically improved technique to detect single nucleotide polymorphisms (SNPs) with different frequency between the control and the disease group. SNP, however, is not an universal disease-marker that can be used in any case. For different ethnicities in particular, it is necessary to clarify the difference of the contribution of the gene. Therefore, data of Asian populations would be as significant, and this Journal is considered to further increase the importance in this field. In clinical applications of gene-based medicine, it is also necessary to carry out a longitudinal study of these candidate genes. Even with the genome-wide study, we cannot apply the information to an individual patient. Genetic taylor-made medicine will become possible only when evidence is obtained by carrying out a longitudinal prospective study on the gene of interest. Recently, a new additional area called ‘epigenetics’ has emerged in the field of complex genetic diseases, including diabetes mellitus. Epigenesis refers to a process that is based on the information marked on the genome after fertilization, primarily in animals. This has been elucidated as a mechanism of cellular function, specifically the pattern of gene expression through change of chromatin structure instead of change in the nucleotide sequences. Biochemical entities of the epigenetic marks include deoxyribonucleic acid (DNA) modifications, such as 5-methylcytosine at CpG sites, and post-translational modifications of histones methylation, acetylation and phosphorylation. These are subject to being erased throughout the entire genome in germ line cells, but it comes to appear again after fertilization, and will change according to the specific cellular environment and differentiation. With the exception of this process, epigenetic status can be determined according to parental origin of the allele for genomic imprinting, and can be determined randomly for X chromosome inactivation. Importantly, epigenetic system ensures two outstanding property at the same time. First, the systems shows robust epigenetic memory that is crucial for maintenance of cellular differentiation states even through the process of somatic cell division. Second, the system applies the flexibility of chromatin states to adaptation and responses to various environmental challenges from outside the cell.