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The DNA methyltransferases (DNMTs), DNMT3A and DNMT3B, catalyze somatic cell lineage\u2010specific DNA methylation, while DNMT3A and DNMT3L catalyze germ cell lineage\u2010specific DNA methylation. How such lineage\u2010 and gene\u2010specific DNA methylation patterns are created remains to be elucidated. To better understand the regulatory mechanisms underlying DNA methylation, we generated transgenic mice that constitutively expressed DNMT3A and DNMT3L, and analyzed DNA methylation, gene expression, and their subsequent impact on ontogeny. All transgenic mice were born normally but died within 20 weeks accompanied with cardiac hypertrophy. Several genes were repressed in the hearts of transgenic mice compared with those in wild\u2010type mice. CpG islands of these downregulated genes were highly methylated in the transgenic mice. This abnormal methylation occurred in the perinatal stage. Conversely, monoallelic DNA methylation at imprinted loci was faithfully maintained in all transgenic mice, except <jats:italic>H19<\/jats:italic>. Thus, the loci preferred by DNMT3A and DNMT3L differ between somatic and germ cell lineages.<\/jats:p>","DOI":"10.1002\/mrd.23137","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T05:05:16Z","timestamp":1551762316000},"page":"614-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-6988","authenticated-orcid":false,"given":"Keisuke","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Bioscience Tokyo University of Agriculture Tokyo Japan"},{"name":"Research Fellow of Japan Society for the Promotion of Science Tokyo 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