Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse

Abstract

Genome-wide epigenetic reprogramming by demethylation occurs in early mouse embryos and primordial germ cells. In early embryos many single-copy sequences become demethylated both by active and passive demethylation, whereas imprinted gene methylation remains unaffected. In primordial germ cells single-copy and imprinted sequences are demethylated, presumably by active demethylation. Here we investigated systematically by bisulphite sequencing the methylation profiles of IAP and Line1 repeated sequence families during preimplantation and primordial germ cell development. Whereas Line1 elements were substantially demethylated during both developmental periods, IAP elements were largely resistant to demethylation, particularly during preimplantation development. This may be desirable in order to prevent IAP retrotransposition, which could cause mutations. In turn, this can result in the transgenerational inheritance of epigenetic states of IAPs, which could lead to heritable epimutations of neighbouring genes through influencing their transcriptional states.

Transcriptional activation of transposable elements in mouse zygotes is independent of Tet3-mediated 5-methylcytosine oxidation

“…However, how the expression of TEs in early preimplantation embryos is controlled remains unknown. Based on the observations that: (1) CpG sites in TEs are highly methylated in sperm genome and are demethylated after fertilization [24][25][26]; (2) the hypomethylated state of these CpG sites is maintained during preimplantation development [25], it is assumed that removal of paternal DNA methylation contributes to TE activation. In this study, we tested this assumption by evaluating the role of Tet3-mediated 5mC oxidation in TE activation.…”

Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin

“…DNA demethylation of these genes is initiated in late migratory PGCs (BE10.5) and completed after arrival to the genital ridge (4E13.5). 18,21 Thus, late migratory PGCs (E10.5-E11.5) show partial DNA demethlylation levels of IAP (B74%), LINE1 (B65%), Mvh and Sycp3 and dynamic demethylation is first detectable in a population of post-migratory PGCs (BE13.5). 18,21 In our bisulfite sequencing results, VSELs, similarly to previously reported data on late migratory PGCs, 18,21 show partial demethylation of the Mvh promoter (B80%, Figure 3b), Sycp3 (B82.1%, Supplementary Figure 4a) and LINE1-5 0 LTR (B65%, Figure 3c).…”

“…19 As a result of these epigenetic changes, early specialized, migratory and post-migratory PGCs show distinguished gene expression and epigenetic signatures. 8,[18][19][20][21] When we focused on expression of genes specific to various PGC developmental stages in addition to genes involved in PGC specification (Figures 2b and c), VSELs highly express Dppa2, Dppa4 and Mvh, which characterize late migratory PGCs (E10.5-11.5) 18,20 (Figure 3a).…”

Genomic imprinting as an adaptative model of developmental plasticity

“…A second wave of demethylation occurs around E11.5 and includes the dramatic and rapid erasure of methylation at imprinted loci [5]. Dogma dictates that this demethylation is complete, and that there is no epigenetic inheritance through meiosis, however, some elements, such as intra-cisternal A particles, can partially escape this methylation reprogramming [6,7].…”