Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues
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TLDR
By mapping base-resolution methylomes in adult mouse tissues at shallow coverage, this work identifies 302,864 tissue-specific differentially methylated regions (tsDMRs) and estimates that >6.7% of the mouse genome is variably methylated, and suggests that epigenetic memory of embryonic development may be retained in adult tissues.Abstract:
Mammalian development requires cytosine methylation, a heritable epigenetic mark of cellular memory believed to maintain a cell's unique gene expression pattern. However, it remains unclear how dynamic DNA methylation relates to cell type-specific gene expression and animal development. Here, by mapping base-resolution methylomes in 17 adult mouse tissues at shallow coverage, we identify 302,864 tissue-specific differentially methylated regions (tsDMRs) and estimate that >6.7% of the mouse genome is variably methylated. Supporting a prominent role for DNA methylation in gene regulation, most tsDMRs occur at distal cis-regulatory elements. Unexpectedly, some tsDMRs mark enhancers that are dormant in adult tissues but active in embryonic development. These 'vestigial' enhancers are hypomethylated and lack active histone modifications in adult tissues but nevertheless exhibit activity during embryonic development. Our results provide new insights into the role of DNA methylation at tissue-specific enhancers and suggest that epigenetic memory of embryonic development may be retained in adult tissues.read more
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Tracing Dynamic Changes of DNA Methylation at Single-Cell Resolution
TL;DR: In this paper, the authors established a reporter of genomic methylation (RGM) that relies on a minimal imprinted gene promoter driving a fluorescent protein, and showed that insertion of RGM proximal to promoter-associated CpG islands reports the gain or loss of DNA methylation.
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Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity
Thomas Dahlet,Thomas Dahlet,Andrea Argüeso Lleida,Andrea Argüeso Lleida,Hala Al Adhami,Hala Al Adhami,Michael Dumas,Michael Dumas,Ambre Bender,Ambre Bender,Richard Patryk Ngondo,Richard Patryk Ngondo,Manon Tanguy,Manon Tanguy,Judith Vallet,Judith Vallet,Ghislain Auclair,Ghislain Auclair,Anaïs F. Bardet,Anaïs F. Bardet,Michael Weber,Michael Weber +21 more
TL;DR: By analyzing severely hypomethylated embryos, the authors uncover multiple functions of DNA methylation that is used as a mechanism of repression for a panel of genes including not only imprinted and germline genes, but also lineage-committed genes and 2-cell genes.
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DNA Methylation: Insights into Human Evolution
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TL;DR: The close interplay between Cytosine-phosphate-Guanine (CpG) methylation and the underlying genome sequence, as well as its evolutionary impact is reviewed, and the latest advances in the field are summarized.
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Tissue-specific DNA demethylation is required for proper B-cell differentiation and function.
Shari Orlanski,Verena Labi,Yitzhak Reizel,Adam Spiro,Michal Lichtenstein,Rena Levin-Klein,Sergei B. Koralov,Yael Skversky,Klaus Rajewsky,Howard Cedar,Yehudit Bergman +10 more
TL;DR: This study inactivated the enzymes responsible for the demethylation reaction in the B-cell lineage and in this manner has shown that this epigenetic mark plays a critical role in development, independently of the many specific transcription factors that direct the selection of genes involved in cell differentiation.
Journal ArticleDOI
Allele-Specific Methylome and Transcriptome Analysis Reveals Widespread Imprinting in the Human Placenta.
Hirotaka Hamada,Hiroaki Okae,Hidehiro Toh,Hatsune Chiba,Hitoshi Hiura,Kenjiro Shirane,Tetsuya Sato,Mikita Suyama,Nobuo Yaegashi,Hiroyuki Sasaki,Takahiro Arima +10 more
TL;DR: This study performed genome-wide allelic DNA methylation analyses of purified trophoblast cells from human placentas and found that more than one-quarter of the transient-in-embryo mDMRs maintained their maternally biased DNAmethylation.
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