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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Journal ArticleDOI
DNA Methylation Landscapes of Human Fetal Development
Roderick C. Slieker,Matthias S Roost,Liesbeth van Iperen,H. Eka D. Suchiman,Elmar W. Tobi,Françoise Carlotti,Eelco J.P. de Koning,P. Eline Slagboom,Bastiaan T. Heijmans,Susana M. Chuva de Sousa Lopes +9 more
TL;DR: The analysis of gene expression data indicated that dynamic DNA methylation was associated with the progressive repression of developmental programs and the activation of genes involved in tissue-specific processes, which provides insight into regulatory elements that guide tissue specification and lead to organ functionality.
Journal ArticleDOI
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence
Tonis Org,Dan Duan,Roberto Ferrari,Amélie Montel-Hagen,Ben Van Handel,Marc A. Kerenyi,Rajkumar Sasidharan,Liudmilla Rubbi,Yuko Fujiwara,Matteo Pellegrini,Stuart H. Orkin,Siavash K. Kurdistani,Hanna K. A. Mikkola +12 more
TL;DR: The results suggest that a unique subset of enhancers in lineage‐specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated.
Book ChapterDOI
Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing.
Charlene Babra Waryah,Colette Moses,Colette Moses,Mahira Arooj,Mahira Arooj,Pilar Blancafort,Pilar Blancafort +6 more
TL;DR: The molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms are summarized and their applications for the locus-specific manipulation of the epigenome are described.
Journal ArticleDOI
MAX is an epigenetic sensor of 5-carboxylcytosine and is altered in multiple myeloma.
Dongxue Wang,Hideharu Hashimoto,Xing Zhang,Xing Zhang,Benjamin G. Barwick,Sagar Lonial,Lawrence H. Boise,Paula M. Vertino,Xiaodong Cheng,Xiaodong Cheng +9 more
TL;DR: Data indicate that MAX can act as a direct epigenetic sensor of E-box cytosine modification states and that local CpG modification and MAX variants converge to modulate the MAX-MYC transcriptional network.
Journal ArticleDOI
Cell Type-Specific Epigenomic Analysis Reveals a Uniquely Closed Chromatin Architecture in Mouse Rod Photoreceptors.
TL;DR: ATAC-seq on mouse rods and their most closely related cell type, cone photoreceptors provides insight into the development and maintenance of photoreceptor identity, and highlights rods as an attractive system for studying the relationship between nuclear organization and local changes in gene regulation.
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