Parental alleles of an imprinted mouse transgene replicate synchronously

Shuster, Michèle; Dhar, Madhu; Olins, Ada L.; Olins, Donald E.; Howell, Carina Y.; Gollin, Susanne M.; Chaillet, J. Richard

doi:10.1002/(sici)1520-6408(1998)23:4<275::aid-dvg3>3.0.co;2-#

Cited by 3 publications

(3 citation statements)

References 26 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study clearly shows that altered replication timing is not needed in order to establish altered methylation imprinting, and conversely that establishing methylation in the Igf2-H19 locus does not alter its replication timing. This is consistent with previous observations that alterations in imprinting status do not necessarily correspond to altered regional replication timing and that parental alleles of imprinted transgenes do not necessarily replicate asynchronously (49)(50)(51)(52).…”

Section: Dissociation Of Replication Timing and Imprint Establishment And Maintenancesupporting

confidence: 93%

Paternal imprints can be established on the maternal Igf2-H19 locus without altering replication timing of DNA

Cerrato

Dean²,

Davies³

et al. 2003

Human Molecular Genetics

View full text Add to dashboard Cite

Genomic imprinting in mammals marks the parental alleles in gametes, resulting in differential gene expression in offspring. A number of epigenetic features are associated with imprinted genes. These include differential DNA methylation, histone acetylation and methylation, subnuclear localization and DNA replication timing. While DNA methylation has been shown to be necessary both for establishment and maintenance of imprinting, the connections with the other types of epigenetic marking systems are not clear. Specifically, it is not known whether the other marking systems, either on their own or in conjunction with DNA methylation, are required for imprinting. Here we show that in the mouse mutant Minute (Mnt) the Igf2-H19 locus acquires a paternal methylation imprint in the maternal germline. DNA methylation of the H19 DMR is established in oogenesis, maintained during postzygotic development on the maternal allele, and erased in primordial germ cells. The fact that a paternal type methylation imprint can also be established in the maternal germline indicates that trans-acting factors that target methylation to this imprinted region are likely to be the same in both germlines. Surprisingly, however, asynchrony of DNA replication of the locus is maintained despite the altered expression and methylation imprint of Igf2 and H19. These results show clearly that replication asynchrony of this region is neither the determinant factor for, nor a consequence of, epigenetic modifications that are critical for genomic imprinting. Replication asynchrony may thus be regulated differently from methylation imprints and have a separate function.

show abstract

Section: Dissociation Of Replication Timing and Imprint Establishment And Maintenancesupporting

confidence: 93%

Paternal imprints can be established on the maternal Igf2-H19 locus without altering replication timing of DNA

Cerrato

Dean²,

Davies³

et al. 2003

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…However, a lack of correlation has been shown in other studies [61,62]. The inherited pattern of asynchronous replication of imprinted genes is maintained in germ cells as in somatic cells, and is not erased in both sexes until the onset of meiosis [63].…”

Section: Asynchronous Dna Replicationmentioning

confidence: 89%

“…Replication timing is another mechanism that can explain the maintenance of differential chromatin states through cell division [58], and the activity state of an imprinted allele has been shown to be correlated with the time of DNA replication [59, 60]. However, a lack of correlation has been shown in other studies [61, 62]. The inherited pattern of asynchronous replication of imprinted genes is maintained in germ cells as in somatic cells, and is not erased in both sexes until the onset of meiosis [63].…”

Section: Asynchronous Dna Replicationmentioning

confidence: 99%

Imprinting in the Germ Line

Mann

2001

STEM CELLS

View full text Add to dashboard Cite

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

show abstract