Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line.

Abstract

Methylation patterns of specific genes have been studied by polymerase chain reaction and found to undergo dynamic changes in the germ line and early embryo. Some CpG sites are methylated in sperm DNA and unmodified in mature oocytes, indicating that the parental genomes have differential methylation profiles. These differences, however, are erased by a series of early embryonic demethylation and postblastula remodification events, which serve to reestablish the basic adult methylation pattern prior to organogenesis. During gametogenesis, all of these sites are unmethylated in primordial germ cells but eventually become remodified by 18.5 days postcoitum in both males and females. The final methylation profile of the mature germ cells is then formed by a multistep process of site-specific demethylation events. These results form a basis for the understanding of the biochemical mechanisms and role of DNA methylation in embryonic development.

Reprogramming of genome function through epigenetic inheritance

“…The initiation of imprinting is confined to the germ line, first with the erasure of existing imprints in primordial germ cells (PGCs) [26][27][28][29] , followed by the initiation of a new set of imprints in the male and female germ lines. It should be noted that whereas methylation of DMRs for some genes results in their repression, in other instances (for example, the Igf2r gene), methylation is essential for gene activation 8,9,16 .…”

“…Alternatively, the erasure of imprints might occur at a specific time and be regulated by a developmental clock. Whatever determines the timing of these events, PGCs by E13.5 possess an equivalent epigenetic state with erased imprints 26,27,44 , and male and female gonads become distinguishable with distinct phenotypes. The erasure of imprints is also observed in EG cells 28 .…”

Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin

“…Differential methylation of cytosine residues in CpG dinucleotides in critical regions of imprinted genes is part of the imprinting process differentiating paternal and maternal alleles (Barlow, 1993). Imprinted genes have been well analysed in terms of genome reprogramming, and it is widely accepted that imprinting memories are erased in PGCs and that DNA methylation is an important factor in this process (Grant et al, 1992;Kafri et al, 1992;Brandeis et al, 1993;Szabo and Mann, 1995b;Kato et al, 1999). Maternally expressed H19 is one of the best-characterized imprinted genes.…”

A new perspective on neural tube defects: Folic acid and microRNA misexpression

“…During embryogenesis, all three major DNA methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) are expressed, the most important being Dnmt1 and Dnmt3b in establishing and maintaining proper genomic methylation (Fan et al, 2001;Jackson et al, 2004). In mammalian embryonic development, prior to implantation, the genome becomes demethylated by the 8-to 16-cell stage, with the inner cell mass undergoing global remethylation at discrete CpG sites before onset of gastrulation (Finnell et al, 2002;Kafri et al, 1992;Santos et al, 2002). This is then followed by the demethylation and transcription of tissue-specific genes during organogenesis (Jackson-Grusby et al, 2001).…”