Meiotic and epigenetic aberrations in Dnmt3L-deficient male germ cells.
The DNA methyltransferase-like protein Dnmt3L is necessary for the establishment of genomic imprints in oogenesis and for normal spermatogenesis (Bourc'his et al., 2001; Hata et al., 2002). Also, a paternally imprinted gene, H19, loses DNA methylation in Dnmt3L-/- spermatogonia (Bourc'his and Bestor, 2004; Kaneda et al., 2004). To determine the reason for the impaired spermatogenesis in the Dnmt3L-/- testes, we have carried out a series of histological and molecular studies. We show here that Dnmt3L-/- germ cells were arrested and died around the early meiotic stage. A microarray-based gene expression-profiling analysis revealed that various gonad-specific and/or sex-chromosome-linked genes were downregulated in the Dnmt3L-/- testes. In contrast, expression of retrovirus-like intracisternal A-particle (IAP) sequences was upregulated; consistent with this observation, a specific IAP copy showed complete loss of DNA methylation. These findings indicate that Dnmt3L regulates germ cell-specific gene expression and IAP suppression, which are critical for male germ cell proliferation and meiosis.
Hata
Kenichiro
K
Department of Integrated Genetics, Division of Human Genetics, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Japan. khata@lab.nig.ac.jp
Kusumi
Maki
M
Yokomine
Takaaki
T
Li
En
E
Sasaki
Hiroyuki
H
D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000502:physiology*; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000473:pathology
C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases