Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues
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
Citations
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Function and information content of DNA methylation
TL;DR: These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation, which is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker.
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Chromatin architecture reorganization during stem cell differentiation
Jesse R. Dixon,Inkyung Jung,Siddarth Selvaraj,Yin Shen,Jessica Antosiewicz-Bourget,Ah Young Lee,Zhen Ye,Audrey Kim,Nisha Rajagopal,Wei Xie,Yarui Diao,Jing Liang,Huimin Zhao,Victor V. Lobanenkov,Joseph R. Ecker,James A. Thomson,Bing Ren +16 more
TL;DR: Mapping genome-wide chromatin interactions in human embryonic stem cells and four human ES-cell-derived lineages reveals extensive chromatin reorganization during lineage specification, providing a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.
Journal ArticleDOI
The diverse roles of DNA methylation in mammalian development and disease
TL;DR: The mechanisms and functions of DNA methylation and demethylation in both mice and humans at CpG-rich promoters, gene bodies and transposable elements are discussed and the dynamic erasure and re-establishment in embryonic, germline and somatic cell development is highlighted.
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Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity
Sébastien A. Smallwood,Heather J. Lee,Heather J. Lee,Christof Angermueller,Felix Krueger,Heba Saadeh,Julian R. Peat,Simon Andrews,Oliver Stegle,Wolf Reik,Wolf Reik,Wolf Reik,Gavin Kelsey,Gavin Kelsey +13 more
TL;DR: In this article, a single-cell bisulfite sequencing (scBS-seq) method was used to accurately measure DNA methylation at up to 48.4% of CpG sites.
Journal ArticleDOI
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
Yimeng Yin,Ekaterina Morgunova,Arttu Jolma,Eevi Kaasinen,Biswajyoti Sahu,Syed Khund-Sayeed,Pratyush Kumar Das,Teemu Kivioja,Kashyap Dave,Fan Zhong,Kazuhiro R. Nitta,Minna Taipale,Alexander Popov,Paul A. Ginno,Silvia Domcke,Silvia Domcke,Jian Yan,Dirk Schübeler,Dirk Schübeler,Charles Vinson,Jussi Taipale,Jussi Taipale +21 more
TL;DR: This work systematically analyzed binding specificities of full-length transcription factors and extended DNA binding domains to unmethylated and CpG-methylated DNA by using methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment).
References
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Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer
Gary C. Hon,R. David Hawkins,Otavia L. Caballero,Christine Lo,Ryan Lister,Mattia Pelizzola,Armand Valsesia,Zhen Ye,Samantha Kuan,Lee Edsall,Anamaria A. Camargo,Brian J. Stevenson,Joseph R. Ecker,Vineet Bafna,Robert L. Strausberg,Robert L. Strausberg,Andrew J. G. Simpson,Andrew J. G. Simpson,Bing Ren,Bing Ren +19 more
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TL;DR: A base-resolution, allele-specific DNA methylation map in the mouse genome is generated, finding parent-of-origin dependent (imprinted) ASM at 1,952 CG dinucleotides and a surprising presence of non-CG methylation in the adult mouse brain, with some showing evidence of imprinting.
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Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal
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Promoter features related to tissue specificity as measured by Shannon entropy
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ChIP-Seq identification of weakly conserved heart enhancers
Matthew J. Blow,David J. McCulley,Zirong Li,Tao Zhang,Jennifer A. Akiyama,Amy Holt,Ingrid Plajzer-Frick,Malak Shoukry,Crystal Wright,Feng Chen,Veena Afzal,James Bristow,Bing Ren,Brian L. Black,Edward M. Rubin,Edward M. Rubin,Axel Visel,Axel Visel,Len A. Pennacchio,Len A. Pennacchio +19 more
TL;DR: Transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint, suggesting that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.
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