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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Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer
TL;DR: This review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamouscell carcinoma in areas for which specific data is available.
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Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution
Isabel Mendizabal,Lei Shi,Thomas Keller,Genevieve Konopka,Todd M. Preuss,Tzung-Fu Hsieh,Enzhi Hu,Zhe Zhang,Bing Su,Soojin V. Yi +9 more
TL;DR: These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions, and their regulatory potential is on par with those of promoter DMRs.
Journal ArticleDOI
DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells
Matthias S Roost,Roderick C. Slieker,Monika Bialecka,Liesbeth van Iperen,Maria Gomes Fernandes,Nannan He,H. Eka D. Suchiman,Karoly Szuhai,Françoise Carlotti,Eelco J.P. de Koning,Christine L. Mummery,Bastiaan T. Heijmans,Susana M. Chuva de Sousa Lopes,Susana M. Chuva de Sousa Lopes +13 more
TL;DR: A transcriptional and DNA methylation atlas covering 21 organs during human fetal development and 6 isogenic induced pluripotent stem cell lines is generated, providing insights in the role of DNA methylisation in lineage commitment and epigenetic reprogramming in humans.
Journal ArticleDOI
GC skew is a conserved property of unmethylated CpG island promoters across vertebrates
TL;DR: It is observed that terminal GC skew is conserved for a subset of vertebrate genes that tend to be located significantly closer to their downstream neighbors, consistent with a role for R-loop formation in transcription termination.
Journal ArticleDOI
Islet cells share promoter hypomethylation independently of expression, but exhibit cell-type-specific methylation in enhancers
Daniel Neiman,Joshua Moss,Merav Hecht,Judith Magenheim,Sheina Piyanzin,A. M. James Shapiro,Eelco J.P. de Koning,Eelco J.P. de Koning,Aharon Razin,Howard Cedar,Ruth Shemer,Yuval Dor +11 more
TL;DR: It is shown that islet cells expressing insulin, glucagon, or somatostatin share a lack of methylation at the promoters of the insulin and glucagon genes, which supports the fundamental role of enhancer methylation in determining cell identity, and has implications for the understanding of islet cell plasticity in diabetes.
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