Relationship between epigenetic regulation, dietary habits, and the developmental origins of health and disease theory.
Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including those during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin. In general, the demethylation of CpG islands induces histone acetylation and associated changes from heterochromatin to euchromatin, and enhances transcriptional activation. These changes are induced by the binding of transcriptional factors to cis-elements located on promoter and enhancer regions and the associated binding of histone acetyl-transferase and the transcription initiation complex. Recent studies have demonstrated novel epigenetic modifications that regulate transcription elongation steps by activating histone acetylation and bromodomain-containing protein 4, which contains two bromodomains to bind acetylated histones, on the gene body (transcribed region). Gene expression alterations induced by carbohydrate signals and by changes in energy balance in the body are regulated by this model. In addition, induction of many metabolic genes, which are induced or reduced in adulthood by malnutrition during developmental stages, by intake of major nutrients, or development of lifestyle diseases in adulthood, are targeted by these novel epigenetic changes. In the present review, we introduce epigenetic regulations and the relationship with nutrient intake, and discuss links between epigenetic regulation and the development of metabolic diseases according to DOHaD.
Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Kofu, Japan.
Kazuki
K
Mochizuki
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Natsuyo
N
Hariya
Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
Kazue
K
Honma
Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
Toshinao
T
Goda
D000107:Acetylation; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004742:Enhancer Elements, Genetic; D004777:Environment; D004782:Environmental Health; D044127:Epigenesis, Genetic; D005247:Feeding Behavior / Q000523:psychology*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
Developmental Origins of Health and Disease; epigenetics; gene body; histone acetylation