Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice.
DNA methylation is generally known to inactivate gene expression. The DNA methyltransferases (DNMTs), DNMT3A and DNMT3B, catalyze somatic cell lineage-specific DNA methylation, while DNMT3A and DNMT3L catalyze germ cell lineage-specific DNA methylation. How such lineage- and gene-specific 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-type 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 H19. Thus, the loci preferred by DNMT3A and DNMT3L differ between somatic and germ cell lineages.
['Sasaki|Keisuke|K|0000-0002-0591-6988', 'Hara|Satoshi|S|', 'Yamakami|Reina|R|', 'Sato|Yusuke|Y|', 'Hasegawa|Saki|S|', 'Kono|Tomohiro|T|', 'Morohaku|Kanako|K|', 'Obata|Yayoi|Y|']
D000818:Animals D006332:Cardiomegaly D018899:CpG Islands D004248:DNA (Cytosine-5-)-Methyltransferases D019175:DNA Methylation D000090205:DNA Methyltransferase 3A D000066630:Ectopic Gene Expression D005260:Female D005854:Germ Cells D008297:Male D051379:Mice D008822:Mice, Transgenic
DNA methyltransferases DNA methylation ontogeny Down’s syndrome genomic imprinting