Dynamic CpG island methylation landscape in oocytes and preimplantation embryos

By Sébastien A. Smallwood, Shin-ichi Tomizawa, Felix Krueger, N. Ruf, N. Carli, A. Segonds-Pichon, Shun Sato, K. Hata, Simon R. Andrews, G. Kelsey. Nature Genetics, 2011

666 citations recorded by the source corpus.

Elucidating how and to what extent CpG islands (CGIs) are methylated in germ cells is essential to understand genomic imprinting and epigenetic reprogramming. Here we present, to our knowledge, the first integrated epigenomic analysis of mammalian oocytes, identifying over a thousand CGIs methylated in mature oocytes. We show that these CGIs depend on DNMT3A and DNMT3L but are not distinct at the sequence level, including in CpG periodicity. They are preferentially located within active transcription units and are relatively depleted in H3K4me3, supporting a general transcription-dependent mechanism of methylation. Very few methylated CGIs are fully protected from post-fertilization reprogramming but, notably, the majority show incomplete demethylation in embryonic day (E) 3.5 blastocysts. Our study shows that CGI methylation in gametes is not entirely related to genomic imprinting but is a strong factor in determining methylation status in preimplantation embryos, suggesting a need to reassess mechanisms of post-fertilization demethylation.

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

View Paper: https://www.semanticscholar.org/paper/9735532b2e1514e635f7b1b6bfad3a1ae7b1cc52

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In Genetics

In Molecular Biology

In Pediatrics, Perinatology and Child Health

Alexander Meissner

Citations in the corpus

Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, neutral): “…DNA demethylation, a subset of maternally derived methylated CpG-rich sequences, including many maternal ICRs and some retroviral repeats such as the intracisternal A particle (IAP) type, remain fully or partially methylated (Lane et al., Cell 15 2003; Smallwood et al., 2011; Smith et al., 2012).”
DNA methylation: a historical perspective. (2022, neutral): “resist preimplantation DNA demethylation and maintain their parent-of-origin specific DNA methylation [299,300].”
A unique regulatory phase of DNA methylation in the early mammalian embryo (2012, background): “Compared to all other genome-wide profiling strategies currently available, RRBS is optimally suited for the low cell numbers that can be obtained from embryonic samples 23–25 .”
Single-Cell DNA Methylome Sequencing and Bioinformatic Inference of Epigenomic Cell-State Dynamics (2015, methodology): “RRBS has also been applied to populations of about 100 cells from mouse embryos and oocytes (Smallwood et al., 2011; Smith et al., 2012), yielding data for 1–2 million CpGs out of the approximately 21.”