Demethylation of the zygotic paternal genome

Mayer, Wolfgang; Niveleau, Alain; Walter, Jörn; Fundele, Reinald; Haaf, Thomas

doi:10.1038/35000656

Cited by 1,195 publications

(629 citation statements)

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“…A previous study found typical demethylation processes in these repetitive sequences in pig preimplantation embryos [15]. Similar results were also found in mouse [20]. In cloned bovine embryos, these repeated regions of the donor genome exhibited aberrant methylation patterns [8].…”

Section: Discussionsupporting

confidence: 81%

Altered imprinted gene expression and methylation patterns in mid-gestation aborted cloned porcine fetuses and placentas

Zhang

Wang

Han

et al. 2014

J Assist Reprod Genet

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Purpose To determine the expression patterns of imprinted genes and their methylation status in aborted cloned porcine fetuses and placentas. Methods RNA and DNA were prepared from fetuses and placentas that were produced by SCNT and controls from artificial insemination. The expression of 18 imprinted genes was determined by quantitative real-time PCR (q-PCR).Bisulfite sequencing PCR (BSP) was conducted to determine the methylation status of PRE-1 short interspersed repetitive element (SINE), satellite DNA and H19 differentially methylated region 3 (DMR3). Results The weight, imprinted gene expression and genomewide DNA methylation patterns were compared between the mid-gestation aborted and normal control samples. The results showed hypermethylation of PRE-1 and satellite sequences, the aberrant expression of imprinted genes, and the hypomethylation of H19 DMR3 occurred in mid-gestation aborted fetuses and placentas. Conclusions Cloned pigs generated by somatic cell nuclear transfer (SCNT) showed a greater ratio of early abortion during mid-gestation than did normal controls because of the incomplete epigenetic reprogramming of the donor cells. Altered expression of imprinted genes and the hypermethylation profile of the repetitive regions (PRE-1 and satellite DNA) may be associated with defective development and early abortion of cloned pigs, emphasizing the importance of epigenetics during pregnancy and implications thereof for patient-specific embryonic stem cells for human therapeutic cloning and improvement of human assisted reproduction.

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Section: Discussionsupporting

confidence: 81%

Altered imprinted gene expression and methylation patterns in mid-gestation aborted cloned porcine fetuses and placentas

Zhang

Wang

Han

et al. 2014

J Assist Reprod Genet

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“…A monoclonal anti-5-methylcytosine antibody was purchased from Eurogentech (MMS-900S-B; Mayer et al, 2000). Antibodies that specifically recognize di-/tri-methylated H3-K9, trimethylated H3-K4, trimethylated H3-K27, dimethylated H3-K36, trimethylated H4-K20, or acetylated H3-K9 residues were all purchased from Upstate Biotechnologies.…”

Section: Antibodies and Immunostainingmentioning

confidence: 99%

Gradual development of a genome‐wide H3‐K9 trimethylation pattern in paternally derived pig pronucleus

Jeong

Yeo

Park

et al. 2007

Developmental Dynamics

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The cytoplasm of a mature oocyte contains many protein complexes that are programmed to restructure incoming sperm chromatins on fertilization. Of the complicated biochemical events that these functional machineries control, the most impressive and important is epigenetic reprogramming. Despite its importance in epigenetic resetting, or "de-differentiation," of gamete genomes back to an incipient status, the mechanisms of epigenetic reprogramming do not seem to be conserved among mammals. Here, we report that, unlike in the mouse, the pig sperm-derived pronucleus is markedly trimethylated at lysine 9 of histone H3 (H3-m 3 K9), which might be associated with preservation of paternally derived cytosine methylation in pig zygotes. The male H3-m 3 K9 pattern is gradually established during pronucleus development, and this process occurs independently of DNA replication. Considering these unique epigenetic features, the pig zygote is, we believe, suited to serve as another model of epigenetic reprogramming that is antithetical to the well-characterized mouse model. Developmental Dynamics 236:1509 -1516, 2007.

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“…During the initial 0-5 h.p.f., the parental genomes exhibit dramatic epigenetic differences. The paternal genome undergoes marked demethylation while the maternal genome, which contains most of the methylation marks associated with imprints, undergoes further de novo methylation 11,12,47 . Species where imprinting is unknown do not show such differential methylation of parental genomes during early development.…”

Section: Genomic Reprogramming In the Zygotementioning

confidence: 99%

“…Loss of function of either of the two genes results in the loss of germ cell lineage in worms. Genome-wide demethylation is also observed in PGCs and in the paternal genome in the zygote 11,12,56 , although it is important to note that whereas the imprints are erased in PGCs, this is not the case during embryonic development.…”

Section: Genomic Reprogramming In the Zygotementioning

confidence: 99%

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Reprogramming of genome function through epigenetic inheritance

Surani

2001

Nature

411

296

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Most cells contain the same set of genes and yet they are extremely diverse in appearance and functions. It is the selective expression and repression of genes that determines the specific properties of individual cells. Nevertheless, even when fully differentiated, any cell can potentially be reprogrammed back to totipotency, which in turn results in re-differentiation of the full repertoire of adult cells from a single original cell of any kind. Mechanisms that regulate this exceptional genomic plasticity and the state of totipotency are being unravelled, and will enhance our ability to manipulate stem cells for therapeutic purposes.

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Demethylation of the zygotic paternal genome

Cited by 1,195 publications

References 9 publications

Altered imprinted gene expression and methylation patterns in mid-gestation aborted cloned porcine fetuses and placentas

Altered imprinted gene expression and methylation patterns in mid-gestation aborted cloned porcine fetuses and placentas

Gradual development of a genome‐wide H3‐K9 trimethylation pattern in paternally derived pig pronucleus

Reprogramming of genome function through epigenetic inheritance

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