The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells

By Stefanie Seisenberger, Simon R. Andrews, Felix Krueger, Julia Arand, Jörn Walter, Fátima Santos, C. Popp, B. Thienpont, W. Dean, Wolf Reik. Molecules and Cells, 2012

922 citations recorded by the source corpus.

Summary Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3a2f9e9f728d97467d7d4027001b1f6ea7c9828c

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Citations in the corpus

Differential methylation analysis for BS-seq data under general experimental design (2016, background): “It often shows abnormality in many diseases such as cancer (Bird, 2002; Reik, 2007; Meissner et al., 2008; Kriaucionis and Heintz, 2009; Teschendorff et al., 2010; Szulwach et al., 2011b; Seisenberger et al., 2012).”
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, positive): “5, the overall CpGmethylation level reduces to 30% in PGCs (Seisenberger et al., 2012).”
Charting a dynamic DNA methylation landscape of the human genome (2013, neutral): “Greyboxes (1–3) are examplesof regions that are static (1 and 2) or that do notmeet the threshold of dynamic (3).”
Transgenerational Epigenetic Inheritance: myths and mechanisms (2014, neutral): “In the germline, where all known imprints appear to be erased, the efficiency of DNA methylation reprogramming of the epigenome has been comprehensively assessed in two recent studies in the mouse (Hackett et al., 2012; Seisenberger et al., 2012).”
A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development (2015, background): “…pathways, genome-wide loss of 5-methylcytosine (5mC) occurs through replication-coupled dilution (Guibert et al., 2012; Kagiwada et al., 2013; Seisenberger et al., 2012) and by conversion of 5mC to 5-hydroxymethylcytosine (5hmC) by TET enzymes (Dawlaty et al., 2013; Hackett et al., 2013;…”
Interpreting thelanguage of histone and DNA modifications (2014, background): “Aided by important technological advances in both sample collection and genome-widemapping capabilities, the dynamics of epigenetic reprogramming in the early stages of development have been reexamined extensively over the past several years (for recent in-depth reviews, see [193,197]).”
A Reference Methylome Database and Analysis Pipeline to Facilitate Integrative and Comparative Epigenomics (2013, background): “During early development of mammalian germ cells, most of the genome is unmethylated, with certain regions retaining methylation despite global epigenetic reprogramming [25].”