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Imprinting in the Germ Line

Section of Mammalian Development, Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA

Key Words. Imprinting • Germ line • Epigenetics • Methylation • Replication timing • Embryonic stem cells

Jeffrey R. Mann, Ph.D., Division of Biology, Beckman Research Institute, 1450 E. Duarte Rd., Duarte, California 91010-3011, USA. Telephone: 626-301-8813; Fax: 626-358-7703; e-mail: jmann{at}coh.org

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.

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