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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Allelic reprogramming of the histone modification H3K4me3 in early mammalian development
Bingjie Zhang,Hui Zheng,Bo Huang,Bo Huang,Wenzhi Li,Yunlong Xiang,Xu Peng,Jia Ming,Xiaotong Wu,Yu Zhang,Qianhua Xu,Wenqiang Liu,Xiaochen Kou,Yanhong Zhao,Wenteng He,Chong Li,Bo Chen,Yuanyuan Li,Qiujun Wang,Jing Ma,Qiangzong Yin,Kehkooi Kee,Anming Meng,Shaorong Gao,Feng Xu,Jie Na,Wei Xie +26 more
TL;DR: A panoramic view of the landscape of H3K4me3, a histone hallmark for transcription initiation, from developing gametes to post-implantation embryos is provided by developing a highly sensitive approach, STAR ChIP–seq, to unveil inheritance and highly dynamic reprogramming of the epigenome in early mammalian development.
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Programming and Inheritance of Parental DNA Methylomes in Mammals
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TL;DR: It is found that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos.
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Transcription factors as readers and effectors of DNA methylation
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TL;DR: Evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA, and the identification of these proteins and the elucidation of their characteristics and the biological consequences are important stepping stones towards a mechanistic understanding of methylation-mediated biological processes.
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Dynamic DNA methylation: In the right place at the right time
TL;DR: Recent findings that delineate 5mC functions in developmental stages and diverse genomic compartments are reviewed as well as discuss the molecular mechanisms that connect transcriptional regulation and5mC.
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Principles of DNA methylation and their implications for biology and medicine.
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TL;DR: Taking advantage of tissue-specific differences, methylation can be used to detect cell death and thereby monitor many common diseases with a simple cell-free circulating-DNA blood test.
References
More filters
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities
Sven Heinz,Christopher Benner,Nathanael J. Spann,Eric Bertolino,Yin C. Lin,Peter Laslo,Jason X. Cheng,Cornelis Murre,Harinder Singh,Harinder Singh,Christopher K. Glass +10 more
TL;DR: It is demonstrated in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions.
Journal ArticleDOI
DNA methylation patterns and epigenetic memory
TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Journal ArticleDOI
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Jesse R. Dixon,Siddarth Selvaraj,Siddarth Selvaraj,Feng Yue,Audrey Kim,Yan-Yan Li,Yin-Zhong Shen,Ming Hu,Jun Liu,Bing Ren,Bing Ren +10 more
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
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