Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development
- Kenji Ichiyanagi1,9,
- Yungfeng Li1,
- Toshiaki Watanabe2,
- Tomoko Ichiyanagi1,
- Kei Fukuda1,3,
- Junko Kitayama4,
- Yasuhiro Yamamoto1,
- Satomi Kuramochi-Miyagawa5,
- Toru Nakano5,
- Yukihiro Yabuta6,7,
- Yoshiyuki Seki7,8,
- Mitinori Saitou6,7 and
- Hiroyuki Sasaki1
- 1Division of Epigenomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan;
- 2Department of Cell Biology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA;
- 3Department of Genetics, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan;
- 4Division of Agricultural Genetics, National Institute of Genetics, Mishima, Sizuoka 411-8540, Japan;
- 5Department of Pathology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
- 6Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;
- 7Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, Kobe, Hyogo 650-0047, Japan;
- 8Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669-1337, Japan
Abstract
In mammals, germ cells undergo striking dynamic changes in DNA methylation during their development. However, the dynamics and mode of methylation are poorly understood for short interspersed elements (SINEs) dispersed throughout the genome. We investigated the DNA methylation status of mouse B1 SINEs in male germ cells at different developmental stages. B1 elements showed a large locus-to-locus variation in methylation; loci close to RNA polymerase II promoters were hypomethylated, while most others were hypermethylated. Interestingly, a mutation that eliminates Piwi-interacting RNAs (piRNAs), which are involved in methylation of long interspersed elements (LINEs), did not affect the level of B1 methylation, implying a piRNA-independent mechanism. Methylation at B1 loci in SINE-poor genomic domains showed a higher dependency on the de novo DNA methyltransferase DNMT3A but not on DNMT3B, suggesting that DNMT3A plays a major role in methylation of these domains. We also found that many genes specifically expressed in the testis possess B1 elements in their promoters, suggesting the involvement of B1 methylation in transcriptional regulation. Taken altogether, our results not only reveal the dynamics and mode of SINE methylation but also suggest how the DNA methylation profile is created in the germline by a pair of DNA methyltransferases.
Footnotes
-
↵9 Corresponding author.
E-mail ichiyanagi{at}bioreg.kyushu-u.ac.jp.
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.123679.111.
- Received March 23, 2011.
- Accepted August 23, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
