Gamete imprinting: setting epigenetic patterns for the next generation

Abstract

Abstract. The acquisition of genomic DNA methylation patterns, including those important for development, begins in the germ line. In particular, imprinted genes are differentially marked in the developing male and female germ cells to ensure parent-of-origin-specific expression in the offspring. Abnormalities in imprints are associated with perturbations in growth, placental function, neurobehavioural processes and carcinogenesis. Based, for the most part, on data from the well-characterised mouse model, the present review will describe recent studies on the timing and mechanisms underlying the acquisition and maintenance of DNA methylation patterns in gametes and early embryos, as well as the consequences of altering these patterns.

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

“…Jaquetta M. Trasler, Montreal Children's Hospital Research Institute Jaquetta Trasler described the mechanisms for establishing and maintaining patterns of DNA methylation in mammalian genomes [Trasler, 2006]. DNA methylation is one of the best-characterized epigenetic mechanisms for modulating gene function.…”

“…The DNA of both male and female primordial germ cells initially undergoes demethylation at about the time the cells enter the embryonic gonads. Remethylation occurs according to different time lines in male and female gametes [Trasler, 2006]. Male germ cells begin to be methylated before birth and continue to be methylated at some sites after birth.…”

“…Several murine DNA methyltransferase (DNMT) genes that play roles in de novo and maintenance DNA methylation have been cloned and characterized [Trasler, 2006]. DNMT1 is involved in maintenance methylation of hemimethylated DNA, and DNMT3A and DNMT3B are involved in de novo methylation during DNA reprogramming.…”

Épimutations héréditaires

“…Il existe en revanche peu de cas documentés chez les mammifères, où les profils de méthylation sont effacés entre chaque génération lors du passage par la lignée germinale. Cette reprogrammation germinale permet de restaurer un état de totipotence, de remettre à zéro les marques d'empreinte parentale et elle réduit les risques de transmission d'épimuta-tions [3]. Des exemples d'épimutations héréditaires ont cependant été décrits chez la souris.…”

Sperme express

“…Cependant, ces modèles cellulaires de différenciation germinale ne reproduisent pas les caractéristiques spatiales et temporelles du développement gamétique in vivo, et se pose légitimement la question de l'intégrité génétique et épigénétique des cellules germinales dérivées des cellules ES et de leur utilisation potentielle en médecine reproductive. Les contraintes d'environnement et de cinétique sont notamment cruciales pour la reprogrammation des profils de méthylation de l'ADN qui accompagnent la différenciation germinale mâle [12].…”