Timing of establishment of paternal methylation imprints in the mouse

• Published in: Genomics (San Diego, Calif.) Vol. 84; no. 6; pp. 952 - 960
• Main Authors: Li, Jing-Yu, Lees-Murdock, Diane J., Xu, Guo-Liang, Walsh, Colum P.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-12-2004; Elsevier
• Subjects: Alleles; Animals; Biological and medical sciences; Differentially methylated region; DNA Methylation; Embryo, Mammalian - cytology; Female; Fundamental and applied biological sciences. Psychology; Gametogenesis - genetics; Gene Expression Regulation, Developmental; Genes. Genome; Genetics of eukaryotes. Biological and molecular evolution; Genomic Imprinting; Germ cells; Germ Cells - growth & development; Germ Cells - metabolism; Gtl2; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Molecular and cellular biology; Molecular genetics; Mouse; Oocytes - physiology; Promoter Regions, Genetic - genetics; Proteins - genetics; ras-GRF1 - genetics; Rasgrf1; Ribonucleoproteins, Small Nuclear - genetics; RNA, Long Noncoding; RNA, Untranslated - genetics; Spermatozoa - physiology; Time Factors; Rasgrf1; DNA methylation; Gtl2; Differentially methylated region; Germ cells; Mouse; Genomics; Rodentia; Germinal cell; Vertebrata; Mammalia; DNA; Timing; Methylation; Rasgrfl
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2004.08.012

Imprinted genes are characterized by predominant expression from one parental allele and differential DNA methylation. Few imprinted genes have been found to acquire a methylation mark in the male germ line, however, and only one of these,
H19, has been studied in detail. We examined methylation of the
Rasgrf1 and
Gtl2 differentially methylated regions (DMR) to determine whether methylation is erased in male germ cells at e12.5 and when the paternal allele acquires methylation. We also compared their methylation dynamics with those of
H19 and the maternally methylated gene
Snrpn. Our results show that methylation is erased on
Rasgrf1, H19, and
Snrpn at e12.5, but that
Gtl2 retains substantial methylation at this stage. Erasure of methylation marks on
Gtl2 appears to occur later in female germ cells to give the unmethylated profile seen in mature MII oocytes. In the male germ line, de novo methylation of
Rasgrf1, Gtl2, and
H19 occurs in parallel between e12.5 and e17.5, but the DMR are not completely methylated until the mature sperm stage, suggesting a methylation dynamic different from that of IAP, L1, and minor satellite sequences, which have been shown to become fully methylated by e17.5 in male germ cells. This study also indicates important differences between different imprinted DMR in timing and extent of methylation in the germ cells.