An international collaborative research group (Note) of Keisuke Yoshida (at the time of research) and Shunsuke Ishii, a collaborative researcher at RIKEN, used mice to control the changes in gene expression and cholesterol in the liver of children by the father's low-protein diet. We clarified the mechanism that induces metabolic changes.

 Recently, the fetal programming hypothesis that "the nutritional status of the parent's generation affects the incidence of childhood diseases, especially lifestyle-related diseases such as diabetes," has been demonstrated molecularly biologically.It is said that this phenomenon occurs when the epigenome (chemically modified gene sequence information) changes and is inherited, but the mechanism is unknown.

 Researchers Ishii and colleagues have shown that the transcription factor ATF7 plays an important role in inducing epigenome changes due to environmental factors such as stress.Therefore, the research group investigated the involvement of ATF7 in the phenomenon that a low-protein diet in paternal mice affects children.

 As a result, when a low-protein diet was given to wild-type male mice, the expression of cholesterol metabolism system genes and other genes was changed in the liver of the child, but male mice with a heterozygous variant of ATF7 (ATF7 is half the amount of wild-type) In the case of the father, no change in gene expression was observed in the child, and it was found that ATF7 is essential for the effect on the child.In addition, when a low-protein diet is given, ATF7 is phosphorylated in the germ cells of the male testis and released from the target gene to cause epigenetic changes (decreased dimethylation levels of histone H3K9), which are changed from sperm to fertilized eggs. The mechanism of inducing changes in gene expression was found.

 This result provides a clue to the scientific elucidation of nutritional conditions that affect the onset of lifestyle-related diseases in children such as diabetes, and in addition to the development of supplements, it is possible to predict metabolic changes in the next generation by measuring epigenome changes in genes. It is supposed to be.

Note: In addition, University of Tsukuba, Osaka University, Kyushu University, University of Tokyo, and Strasbourg University participated.

Paper information:[Molecular Cell] ATF 7-dependent epigenetic change is required for intergenerational effect of paternal low-protein diet

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