Imprinting in the Germ Line

Abstract

Genomic imprinting is an epigenetic system of gene regulation in mammals. It determines the parent-of-origin-dependent expression of a small number of imprinted genes during development, i.e., the maternal allele is inactive while the paternal is active, or vice versa. Imprinting is imparted in the germ line and involves differential DNA methylation such that particular DNA regions become methylated in one sex of germ line but not in the other. Inheritance of these differential egg and sperm methylation states is then transmitted to somatic cells, where they lead to differential maternal and paternal allelic activity, or monoallelic expression. Increasing evidence indicates that the inherited and stable differential allelic methylation regulates monoallelic expression by influencing the activity of gene regulatory elements-for one allele the element is switched off by methylation, while for the other the element is left potentially active by the lack of methylation. An interesting feature of the germ line is that, despite the presence of genomic imprinting, either as imprints inherited from the zygote or as new imprints imparted according to germ cell sex, imprinted genes are biallelically expressed as if imprints were not present. One explanation for this observation is that imprints have no influence over the germ cell's transcriptional machinery, i.e., imprinting may be neutralized in the germ cell lineage. This phenomenon may have a common basis with other unique features of the germ line, such as totipotency, perhaps in some unique aspect of chromatin structure. Stem

Very small embryonic-like stem cells in adult tissues—Potential implications for aging

“…We hypothesize that the problem with providing such evidence could be explained by the possibility that all PSC that reside in adult tissues erase "somatic imprint" that means different methylation of some maternally and paternally inherited genes (e.g., H19, Igf-2, Igf-2R, Snrpn) (Lee et al, 2002;Mann, 2001). For example, Igf-2 is expressed from paternal and H19 from maternal chromosome.…”

“…The erasure of somatic imprint on these genes by demethylation process protects developing organism from parthenogenesis and teratoma formation. However, on the other hand, prevents the contribution of surviving into adulthood PSC to complete blastocyst development (Lee et al, 2002;Mann, 2001). …”

“…The phenomenon of erasure of the somatic imprint was studied extensively in a case of epiblast derived PGC (Lee et al, 2002;Mann, 2001). Accordingly, shortly before the epiblast is about to give rise to all three germ layers (ectoderm, mesoderm and endoderm), the first morphologically identifiable precursors of primordial germ cells (PGC) in mice become specified ~ 6.0-6.5 days post conception (dpc) in the proximal part of the epiblast as the first population of stem cells in the embryo at the beginning of gastrulation (McLaren, 1992;McLaren, 2003).…”

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

“…To explain this phenomenon at the molecular level, it is known that the pluripotency of PGC nuclei depends on the methylation status of genomic imprinted genes (e.g., H19, Igf-2, Igf-2R, Snrpn; Mann, 2001;Yamazaki et al, 2003). PGC until 9.5 dpc display a somatic imprint (paternal and maternal pattern of methylation) of H19, Igf-2, Igf-2R, Snrpn-that is crucial to maintain their pluripotency.…”

Reprogramming of genome function through epigenetic inheritance

“…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 .…”