エピジェネティックスと生命現象の制御

抄録

Epigenetics has recently been accepted to play a role in normal development and the expression of various genes; however, epigenetic changes have been implicated in the pathogenesis of a number of diseases, such as cancer, aging, metabolic diseases, psychogenetic diseases, and inflammatory diseases. The main mechanism of epigenetics involves the modification of histones and methylation of DNA. In this review, we describe interactions between epigenetic changes and diseases. We also highlight the epigenetic theory of presbycusis and the future direction of otological epigenetics.

The methylation of DNA without alterations to the sequence of genomic DNA, achieved by the addition of a methyl group through DNA methyltransferase to the 5-position of the cytosine base, inhibited the transcription of specific genes. DNA is also wrapped around the core histone, which is an octamer composed of H2A, H2B, H3, and H4. The amino terminals, which extended from core histones, were altered by methylation, phosphorylation or phosphorylation.

Variations in gene expression or its suppression has been reported in cancer tissues, and epigenetics is closely associated, such as DNA methylation abnormalities and the histone protein modification anomaly. In addition, aberrant DNA methylation with different excess or hypomethylation is observed.

In the modern aging society, reduced immune responses, chronic inflammation, and the atrophy of muscle tissue, accompanied by an increase in the incidence of cancer have become major public health issues. Monozygotic twin studies revealed differences between the acetylation and methylation levels of H3 and H4 according to age. It was assumed that exogenous factors, such as smoking and physical exercises, and endogenous factors, such as diet are involved. Oxidative stress of DNA, the accumulation of cell mutations, hormonal environment, and apoptosis trigger the abnormal differentiation of neoplastic cells. We additionally described the relationships between epigenetics and psychosis, metabolic diseases, and inflammatory diseases.

We examined histone modifications in the inner ear using an aged mouse model. Degeneration was the most severe in spiral ganglion cells and the organ of Corti at the basal turn. Acetylation switched to methylation in the organ of Corti and spiral ganglion cells during aging. Histone modifications are known to play a critical role in neuro-degeneration. Our results suggest that epigenetic changes are involved in the process of presbycusis.