Dynamic reprogramming of DNA methylation in the early mouse embryo.

By Fátima Santos, B. Hendrich, Wolf Reik, W. Dean. Developmental Biology, 2002

1,249 citations recorded by the source corpus.

Dynamic epigenetic modification of the genome occurs during early development of the mouse. Active demethylation of the paternal genome occurs in the zygote, followed by passive demethylation during cleavage stages, and de novo methylation, which is thought to happen after implantation. We have investigated these processes by using indirect immunofluorescence with an antibody to 5-methyl cytosine. In contrast to previous work, we show that demethylation of the male pronucleus is completed within 4 h of fertilisation. This activity is intricately linked with and not separable from pronucleus formation. In conditions permissive for polyspermy, up to five male pronuclei underwent demethylation in the same oocyte. Paternal demethylation in fertilised oocytes deficient for MBD2, the only candidate demethylase, occurred normally. Passive loss of methylation occurred in a stepwise fashion up to the morulae stage without any evidence of spatial compartmentalisation. De novo methylation was observed specifically in the inner cell mass (ICM) but not in the trophectoderm of the blastocyst and hence may have an important role in early lineage specification. This is the first complete and detailed analysis of the epigenetic reprogramming cycle during preimplantation development. The three phases of methylation reprogramming may have roles in imprinting, the control of gene expression, and the establishment of nuclear totipotency.

Subfields: Genetics, Molecular Biology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/4657b748f1aba75d489bb80cf5031f424c669c7d

How researchers see this paper

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In Genetics

1. Yi Zhang
2. Wolf Reik
3. E. Li
4. W. Dean
5. Jörn Walter
6. Alexander Meissner
7. Fátima Santos
8. Eric J. Richards

In Molecular Biology

1. Yi Zhang
2. Hao Wu
3. Wolf Reik
4. E. Li
5. Alexander Meissner
6. W. Dean
7. Aviv Regev
8. K. Hochedlinger

In Pediatrics, Perinatology and Child Health

1. Yi Zhang
2. E. Li
3. Wolf Reik
4. Jörn Walter
5. W. Dean
6. Fátima Santos
7. Alexander Meissner
8. Eric J. Richards

Citations in the corpus

• A unique regulatory phase of DNA methylation in the early mammalian embryo (2012, background): “Active demethylation is expected to occur prior to pronuclear fusion or the completion of DNA synthesis 11,33 .”
• Active DNA demethylation: many roads lead to Rome (2010, background): “Consistent with this notion, mouse oocytes can demethylate multiple male pronucle”
• Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse (2003, methodology): “This suggests that active demethylation of most of the sperm copies has occurred in the zygote, consistent with the large-scale demethylation in the zygote seen by immunofluorescence (Mayer et al., 2000; Dean et al., 2001; Santos et al., 2002).”
• The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells (2012, methodology): “…12 cycles and size selected by gel extraction for fragments between 200 bp and 250 bp. Immunofluorescence Antibody staining against Np95 (Th10, gift from Haruhiko Koseki) and Dnmt1 (sc-20701, Santa Cruz Biotechnology) was performed as previously described (Santos et al., 2003) with modifications.”
• Epigenetic reprogramming in mouse primordial germ cells. (2002, background): “These observations prove conclusively that PGCs are not exempt from genome wide de novo methylation which begins in inner cell mass cells of the blastocyst (Santos et al., 2002).”
• The mammalian epigenome. (2007, background): “The maternal genome subsequently becomes demethylated, presumably throughapassiveDNA replicationmechanism (Reik et al., 2001; Santos et al., 2002).”
• The maternal-to-zygotic transition: a play in two acts (2009, background): “Immediately after fertilization, the protamines (see Glossary, Box 1) that densely package the sperm DNA are replaced with maternally derived histones (Nonchev and Tsanev, 1990) that are more acetylated than those associated with the maternal pronucleus (Adenot et al., 1997; Santos et al., 2002).”
• Establishment and Maintenance of Genomic Methylation Patterns in Mouse Embryonic Stem Cells by Dnmt3a and Dnmt3b (2003, background): “De novo methylation activity is present mainly in embryonic stem (ES) cells and embryonal carcinoma cells, early postimplantation embryos, and developing germ cells, whereas it is largely suppressed in differentiated somatic cells (22, 24, 41 , 43).”
• DNA hypomethylation and human diseases. (2007, background): “In mouse embryonic development waves of rapid hypomethylation are observed post-fertilisation prior to the re-establishment of methylation patterns [116].”