The H19 Imprinting Control Region Mediates Preimplantation Imprinted Methylation of Nearby Sequences in Yeast Artificial Chromosome Transgenic Mice

被引:11
作者
Okamura, Eiichi [1 ]
Matsuzaki, Hitomi [2 ]
Sakaguchi, Ryuuta [1 ]
Takahashi, Takuya [1 ]
Fukamizu, Akiyoshi [2 ,3 ]
Tanimoto, Keiji [2 ,3 ]
机构
[1] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki, Japan
[2] Univ Tsukuba, Fac Life & Environm Sci, Tsukuba, Ibaraki, Japan
[3] Univ Tsukuba, Life Sci Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki, Japan
基金
日本学术振兴会;
关键词
ENHANCER-BLOCKING ACTIVITY; DE-NOVO METHYLATION; BETA-GLOBIN LOCUS; HISTONE H3 METHYLTRANSFERASE; BECKWITH-WIEDEMANN SYNDROME; MALE GERM-CELLS; DNA METHYLATION; FUNCTIONAL-CHARACTERIZATION; BINDING SEQUENCES; ERYTHROID-CELLS;
D O I
10.1128/MCB.01003-12
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the mouse Igf2/H19 imprinted locus, differential methylation of the imprinting control region (H19 ICR) is established during spermatogenesis and is maintained in offspring throughout development. Previously, however, we observed that the paternal H19 ICR, when analyzed in yeast artificial chromosome transgenic mice (YAC-TgM), was preferentially methylated only after fertilization. To identify the DNA sequences that confer methylation imprinting, we divided the H19 ICR into two fragments (1.7 and 1.2 kb), ligated them to both ends of a lambda DNA fragment into which CTCF binding sites had been inserted, and analyzed this in YAC-TgM. The maternally inherited lambda sequence, normally methylated after implantation in the absence of H19 ICR sequences, became hypomethylated, demonstrating protective activity against methylation within the ICR. Meanwhile, the paternally inherited lambda sequence was hypermethylated before implantation only when a 1.7-kb fragment was ligated. Consistently, when two subfragments of the H19 ICR were individually investigated for their activities in YAC-TgM, only the 1.7-kb fragment was capable of introducing paternal allele-specific DNA methylation. These results show that postfertilization methylation imprinting is conferred by a paternal allele-specific methylation activity present in a 1.7-kb DNA fragment of the H19 ICR, while maternal allele-specific activities protect the allele from de novo DNA methylation.
引用
收藏
页码:858 / 871
页数:14
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