title: Age- and sex-dependent DNA hypomethylation controlled by growth hormone in mouse liver.
abstract: In mammals, differences in liver function and aging have been observed between sexes; however, the epigenetic mechanisms underlying such differences remain largely unexplored. In this study, we investigated sex- and age-dependent DNA methylation status in the mouse liver. We analyzed 90 known sex-differentially expressed genes, and identified sex-dependent methylation in Zfp809, Hsd3b5, Treh, Cxcl11, Cyp17a1, and Nnmt genes. After 4 weeks of age, we noted the gradual establishment of sex-dependent hypomethylation in each of these genes in either males or females. The exposure of male mice to female-like growth hormone (GH) profile repressed male-predominant hypomethylation and promoted female-predominant hypomethylation. The occurrence of age-dependent hypomethylation, including at loci for which we also observed sex-dependent changes in DNA methylation, was accompanied by the downregulation of DNMT3A/B. In addition, we found that age-dependent hypomethylation was promoted through liver regeneration induced by partial hepatectomy, suggesting that DNMT activities were not enough to retain methylation levels. In conclusion, our results demonstrate that sex-dependent GH profiles influence the age-progressive hypomethylation under decreased DNMT3A/B levels in certain regions of the genome.
authors.affiliation: Laboratory of Cellular Biochemistry, Department of Animal Resource Science/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takasugi
authors.forename: Koji
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Arai
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D056426:Genetic Loci / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D012727:Sex Characteristics; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D013006:Growth Hormone; D000097584:DNA Methyltransferase 3B; C000715535:Dnmt3a protein, mouse