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
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
ChIP-seq accurately predicts tissue-specific activity of enhancers
Axel Visel,Matthew J. Blow,Matthew J. Blow,Zirong Li,Tao Zhang,Jennifer A. Akiyama,Amy Holt,Ingrid Plajzer-Frick,Malak Shoukry,Crystal Wright,Feng Chen,Veena Afzal,Bing Ren,Edward M. Rubin,Edward M. Rubin,Len A. Pennacchio,Len A. Pennacchio +16 more
TL;DR: In this paper, the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue.
Journal ArticleDOI
Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma
James G. Herman,Farida Latif,Yongkai Weng,Michael I. Lerman,Berton Zbar,Song-Yuan Liu,D Samid,D S Duan,James R. Gnarra,W.M. Linehan +9 more
TL;DR: The findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers.
Journal ArticleDOI
Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells
Ryan Lister,Mattia Pelizzola,Yasuyuki S. Kida,R. David Hawkins,Joseph R. Nery,Gary C. Hon,Jessica Antosiewicz-Bourget,Jessica Antosiewicz-Bourget,Ronan C. O'Malley,Rosa Castanon,Sarit Klugman,Michael Downes,Ruth T. Yu,Ron Stewart,Ron Stewart,Bing Ren,Bing Ren,James A. Thomson,Ronald M. Evans,Joseph R. Ecker +19 more
TL;DR: The first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells are reported.
Journal ArticleDOI
A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
Richard M. Myers,John A. Stamatoyannopoulos,Michael Snyder,Ian Dunham,Ross C. Hardison,Bradley E. Bernstein,Bradley E. Bernstein,Thomas R. Gingeras,W. James Kent,Ewan Birney,Barbara J. Wold,Gregory E. Crawford,Charles B. Epstein,Noam Shoresh,Jason Ernst,Jason Ernst,Tarjei S. Mikkelsen,Pouya Kheradpour,Pouya Kheradpour,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Timothy Durham,Manching Ku,Thanh Truong,Lucas D. Ward,Lucas D. Ward,Robert C. Altshuler,Michael F. Lin,Michael F. Lin,Manolis Kellis,Manolis Kellis,Carrie A. Davis,Philipp Kapranov,Alexander Dobin,Chris Zaleski,Felix Schlesinger,Philippe Batut,Sudipto K. Chakrabortty,Sonali Jha,Wei Lin,Jorg Drenkow,Huaien Wang,Kim Bell,Ian Bell,Hui Gao,Erica Dumais,Jacqueline Dumais,Stylianos E. Antonarakis,Catherine Ucla,Christelle Borel,Roderic Guigó,Sarah Djebali,Julien Lagarde,Colin Kingswood,Paolo Ribeca,Micha Sammeth,Tyler Alioto,Angelika Merkel,Hagen Tilgner,Piero Carninci,Yoshihide Hayashizaki,Timo Lassmann,Hazuki Takahashi,Rehab F. Abdelhamid,Gregory J. Hannon,Katalin Toth Fejes,Jonathan B. Preall,Assaf Gordon,Vihra Sotirova,Alexandre Reymond,Cédric Howald,Emilie Aït Yahya Graison,Jacqueline Chrast,Yijun Ruan,Xiaoan Ruan,Atif Shahab,Wan Ting Poh,Chia-Lin Wei,Terrence S. Furey,Alan P. Boyle,Nathan C. Sheffield,Lingyun Song,Yoichiro Shibata,Teresa Vales,Deborah R. Winter,Zhancheng Zhang,Darin London,Tianyuan Wang,Damian Keefe,Vishwanath R. Iyer,Bum Kyu Lee,Ryan M. McDaniell,Zheng Liu,Anna Battenhouse,Akshay Bhinge,Jason D. Lieb,Linda L. Grasfeder,Kimberly A. Showers,Paul G. Giresi,Seul K.C. Kim,Christopher Shestak,Florencia Pauli,Timothy E. Reddy,Jason Gertz,E. Christopher Partridge,Preti Jain,Rebekka O. Sprouse,Anita Bansal,Barbara N. Pusey,Michael Muratet,Katherine E. Varley,Kevin M. Bowling,Kimberly M. Newberry,Amy S. Nesmith,Jason A. Dilocker,Stephanie L. Parker,Lindsay L. Waite,Krista Thibeault,Kevin Roberts,Devin Absher,Ali Mortazavi,Brian Williams,Georgi K. Marinov,Diane Trout,Brandon King,Kenneth McCue,Anthony Kirilusha,Gilberto DeSalvo,Katherine Aylor Fisher,Henry Amrhein,Shirley Pepke,Jost Vielmetter,Gavin Sherlock,Arend Sidow,Serafim Batzoglou,Rami Rauch,Anshul Kundaje,Max Libbrecht,Elliott H. Margulies,Stephen C. J. Parker,Laura Elnitski,Eric D. Green,Tim Hubbard,Jennifer Harrow,Stephen M. J. Searle,Felix Kokocinski,Felix Kokocinski,Browen Aken,Adam Frankish,Toby Hunt,Gloria Despacio-Reyes,M. Kay,Gaurab Mukherjee,Alexandra Bignell,Gary Saunders,Veronika Boychenko,Michael R. Brent,M. van Baren,Randall H. Brown,Mark Gerstein,Mark Gerstein,Ekta Khurana,Suganthi Balasubramanian,Hugo Y. K. Lam,Philip Cayting,Philip Cayting,R. Robilotto,Zhi Lu,Thomas Derrien,Andrea Tanzer,David G. Knowles,Marco Mariotti,David Haussler,Rachel A. Harte,Mark Diekhans,Michael F. Lin,Michael F. Lin,Alfonso Valencia,Michael L. Tress,Stephen G. Landt,Stephen G. Landt,Debasish Raha,Minyi Shi,Ghia Euskirchen,Fabian Grubert,Maya Kasowski,Jin Lian,Phil Lacroute,Youhan Xu,Hannah Monahan,Dorrelyn Patacsil,Teri Slifer,Xinqiong Yang,Alexandra Charos,Brian Reed,Linfeng Wu,Raymond K. Auerbach,Lukas Habegger,Manoj Hariharan,Joel Rozowsky,Alexej Abyzov,Sherman M. Weissman,Kevin Struhl,Nathan Lamarre-Vincent,Marianne Lindahl-Allen,Benoit Miotto,Zarmik Moqtaderi,Joseph D. Fleming,Peter E. Newburger,Peggy J. Farnham,Peggy J. Farnham,Seth Frietze,Seth Frietze,Henriette O'Geen,Xiaoqin Xu,Kim Blahnik,Alina R. Cao,Sushma Iyengar,Rajinder Kaul,Robert E. Thurman,Hao Wang,Patrick A. Navas,Richard Sandstrom,Peter J. Sabo,Molly Weaver,Theresa K. Canfield,Kristen Lee,Shane Neph,Vaughan Roach,Alex Reynolds,Audra K. Johnson,Eric Rynes,Erika Giste,Shinny Vong,Jun Neri,Tristan Frum,Eric D. Nguyen,Abigail K. Ebersol,Minerva E. Sanchez,Hadar H. Sheffer,Dimitra Lotakis,Eric Haugen,Richard Humbert,Tanya Kutyavin,Tony Shafer,William Stafford Noble,Job Dekker,Bryan R. Lajoie,Amartya Sanyal,Kate R. Rosenbloom,Timothy R. Dreszer,Brian J. Raney,Galt P. Barber,Laurence R. Meyer,Cricket A. Sloan,Venkat S. Malladi,Melissa S. Cline,Katrina Learned,Vanessa K. Swing,Ann S. Zweig,Brooke Rhead,Pauline A. Fujita,Krishna M. Roskin,Donna Karolchik,Robert M. Kuhn,Steven P. Wilder,Daniel Sobral,Javier Herrero,Kathryn Beal,Margus Lukk,Alvis Brazma,Juan M. Vaquerizas,Nicholas M. Luscombe,Peter J. Bickel,Nathan Boley,James B. Brown,Qiang Li,Haiyan Huang,Andrea Sboner,Kevin Y. Yip,Chao Cheng,Koon-Kiu Yan,Nitin Bhardwaj,Jing Wang,Lucas Lochovsky,Justin Jee,Theodore Gibson,Jing Leng,Jiang Du,Robert S. Harris,Giltae Song,Webb Miller,Bernard B. Suh,Benedict Paten,Michael M. Hoffman,Orion J. Buske,Zhiping Weng,Xianjun Dong,Jie Wang,Hualin Xi,Scott A. Tenenbaum,Frank Doyle,Sridar V. Chittur,Luiz O. F. Penalva,Thomas D. Tullius,Kevin P. White,Subhradip Karmakar,Alec Victorsen,Nader Jameel,Nick Bild,Robert L. Grossman,Patrick J. Collins,Nathan D. Trinklein,Morgan C. Giddings,Morgan C. Giddings,Jainab Khatun,Christopher W. Maier,Ting Wang,Troy W. Whitfield,Xian Chen,Yanbao Yu,Harsha P. Gunawardena,Elise A. Feingold,Rebecca F. Lowdon,Laura A.L. Dillon,Peter J. Good,Brian A. Risk +328 more
TL;DR: An overview of the project and the resources it is generating and the application of ENCODE data to interpret the human genome are provided.
Journal ArticleDOI
A map of the cis-regulatory sequences in the mouse genome
Yin Shen,Feng Yue,David F. McCleary,Zhen Ye,Lee Edsall,Samantha Kuan,Ulrich Wagner,Jesse R. Dixon,Jesse R. Dixon,Leonard Lee,Victor V. Lobanenkov,Bing Ren,Bing Ren +12 more
TL;DR: It is shown that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters, which provides a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
Related Papers (5)
Human DNA methylomes at base resolution show widespread epigenomic differences
Ryan Lister,Mattia Pelizzola,Robert H. Dowen,R. David Hawkins,Gary C. Hon,Julian Tonti-Filippini,Joseph R. Nery,Leonard Lee,Zhen Ye,Que Minh Ngo,Lee Edsall,Jessica Antosiewicz-Bourget,Jessica Antosiewicz-Bourget,Ron Stewart,Ron Stewart,Victor Ruotti,Victor Ruotti,A. Harvey Millar,James A. Thomson,Bing Ren,Bing Ren,Joseph R. Ecker +21 more