Developmental Origins of Health and Disease (DOHaD)

Kazuki Mochizuki, Natsuyo Hariya, Takeo Kubota, Mochizuki, Kazuki, Hariya, Natsuyo, Kubota, Takeo

Epigenetic memories are acquired information included in the chromatin or DNA such as methylation and histone modifications. Recent studies suggest that epigenetic memories determine the types of differentiated cells in each tissue. Moreover, the development of metabolic diseases induced by environmental factors during development is controlled by epigenetic regulation rather than the genetic regulation such as DNA sequence-dependent transcriptional regulation. In general, the demethylation of CpG islands induces histone acetylation, associated changes from heterochromatin to euchromatin, and enhances transcriptional activation. Under the classical model of epigenetics, these changes are induced by the binding of transcriptional factors to cis-elements located on promoter/enhancer regions and the associated binding of histone acetyl-transferase and the transcription initiation complex. This model is dependent on epigenetics in the promoter/enhancer region and is used to explain the induction of genes by lipophilic nutrients such as vitamin A, vitamin D, and unsaturated fatty acid metabolites. However, recent studies have demonstrated that epigenetics in the gene body (transcribed region) also regulate transcription. This novel model postulates that histone acetylation and bromodomain-containing protein 4, which contains two bromodomains to bind acetylated histones, on the gene body enhance transcriptional elongation. Gene expression alterations induced by carbohydrate signals and changes to energy balance in the body accompanied by the intake of major nutrients are also regulated by this model. In this section, we introduce these epigenetic regulations and their relationship with nutrient intake and discuss the link between epigenetic regulation and the development of metabolic diseases.