Epigenomics

  • Article
    | Open Access

    Ibrutinib, a Bruton tyrosine kinase inhibitor, provides effective treatment for chronic lymphocytic leukemia (CLL). Here, the authors describe time-dependent molecular changes to malignant cells and to the immune system in patients undergoing ibrutinib therapy, with can be used for therapy monitoring.

    • André F. Rendeiro
    • , Thomas Krausgruber
    • , Nikolaus Fortelny
    • , Fangwen Zhao
    • , Thomas Penz
    • , Matthias Farlik
    • , Linda C. Schuster
    • , Amelie Nemc
    • , Szabolcs Tasnády
    • , Marienn Réti
    • , Zoltán Mátrai
    • , Donát Alpár
    • , Csaba Bödör
    • , Christian Schmidl
    •  & Christoph Bock
  • Article
    | Open Access

    DNA methylation is associated with complex traits and the expression of genes and proteins. Here, Zaghlool et al. perform epigenome-wide association studies for 1,123 plasma proteins, replicate obtained protein (p)QTMs in an independent cohort and find overlap of pQTMs with expression QTMs and previously reported disease associations.

    • Shaza B. Zaghlool
    • , Brigitte Kühnel
    • , Mohamed A. Elhadad
    • , Sara Kader
    • , Anna Halama
    • , Gaurav Thareja
    • , Rudolf Engelke
    • , Hina Sarwath
    • , Eman K. Al-Dous
    • , Yasmin A. Mohamoud
    • , Thomas Meitinger
    • , Rory Wilson
    • , Konstantin Strauch
    • , Annette Peters
    • , Dennis O. Mook-Kanamori
    • , Johannes Graumann
    • , Joel A. Malek
    • , Christian Gieger
    • , Melanie Waldenberger
    •  & Karsten Suhre
  • Article
    | Open Access

    The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.

    • Katharina V. Schulze
    • , Shanker Swaminathan
    • , Sharon Howell
    • , Aarti Jajoo
    • , Natasha C. Lie
    • , Orgen Brown
    • , Roa Sadat
    • , Nancy Hall
    • , Liang Zhao
    • , Kwesi Marshall
    • , Thaddaeus May
    • , Marvin E. Reid
    • , Carolyn Taylor-Bryan
    • , Xueqing Wang
    • , John W. Belmont
    • , Yongtao Guan
    • , Mark J. Manary
    • , Indi Trehan
    • , Colin A. McKenzie
    •  & Neil A. Hanchard
  • Article
    | Open Access

    N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are eukaryotic mRNA modifications. Here the authors develop m6A-Crosslinking-Exonuclease-sequencing to map quantitative methylome changes at single-base-resolution after individually knocking out each known methyltransferase or demethylase.

    • Casslynn W. Q. Koh
    • , Yeek Teck Goh
    •  & W. S. Sho Goh
  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    • , Vasavi Sundaram
    •  & Ting Wang
  • Article
    | Open Access

    An understanding of the ancestral state of the neural crest (NC) gene regulatory network (GRN) gives insight into vertebrate evolution. Here, the authors use transcriptomic and chromatin accessibility analyses of the lamprey NC, as well as cross-species enhancer assays, to identify GRN elements conserved throughout vertebrates.

    • Dorit Hockman
    • , Vanessa Chong-Morrison
    • , Stephen A. Green
    • , Daria Gavriouchkina
    • , Ivan Candido-Ferreira
    • , Irving T. C. Ling
    • , Ruth M. Williams
    • , Chris T. Amemiya
    • , Jeramiah J. Smith
    • , Marianne E. Bronner
    •  & Tatjana Sauka-Spengler
  • Article
    | Open Access

    Single-cell ATAC-seq data is challenging to analyse for reasons such as high dimensionality and sparsity. Here, the authors develop SCALE, a deep learning method that leverages latent feature extraction for various tasks of scATACseq data analysis.

    • Lei Xiong
    • , Kui Xu
    • , Kang Tian
    • , Yanqiu Shao
    • , Lei Tang
    • , Ge Gao
    • , Michael Zhang
    • , Tao Jiang
    •  & Qiangfeng Cliff Zhang
  • Article
    | Open Access

    Age-related tissue alterations have been associated with a decline in stem cell number and function. Here the authors report a single cell multi-omics study of mouse muscle stem cells, combining single cell transcriptome and DNA methylome profiling and find that aged cells have a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions.

    • Irene Hernando-Herraez
    • , Brendan Evano
    • , Thomas Stubbs
    • , Pierre-Henri Commere
    • , Marc Jan Bonder
    • , Stephen Clark
    • , Simon Andrews
    • , Shahragim Tajbakhsh
    •  & Wolf Reik
  • Article
    | Open Access

    Differentially methylated CpGs can inform on disease mechanisms and be useful as biomarkers. Here, the authors perform GWAS for DNA methylation in whole blood, cis- and trans-meQTL mapping, followed by Mendelian randomization analysis that links meQTLs with cardiovascular diseases.

    • Tianxiao Huan
    • , Roby Joehanes
    • , Ci Song
    • , Fen Peng
    • , Yichen Guo
    • , Michael Mendelson
    • , Chen Yao
    • , Chunyu Liu
    • , Jiantao Ma
    • , Melissa Richard
    • , Golareh Agha
    • , Weihua Guan
    • , Lynn M. Almli
    • , Karen N. Conneely
    • , Joshua Keefe
    • , Shih-Jen Hwang
    • , Andrew D. Johnson
    • , Myriam Fornage
    • , Liming Liang
    •  & Daniel Levy
  • Article
    | Open Access

    Demethylation of the genome is found in cancer. Here, the authors show that genomic demethylation entails changes in promoter methylation and gene expression associated with immune escape and suggest that the epigenetic alterations may be an important determinant of responses to immunotherapy.

    • Hyunchul Jung
    • , Hong Sook Kim
    • , Jeong Yeon Kim
    • , Jong-Mu Sun
    • , Jin Seok Ahn
    • , Myung-Ju Ahn
    • , Keunchil Park
    • , Manel Esteller
    • , Se-Hoon Lee
    •  & Jung Kyoon Choi
  • Article
    | Open Access

    In prostate cancer, chromatin structure can impact the transcriptome. Here, the authors develop high resolution chromatin interaction maps in prostate cancer cells using in situ Hi-C, revealing prostate cancer-specific TADs and enhancer-promoter loops surrounding the androgen receptor (AR) locus.

    • Suhn Kyong Rhie
    • , Andrew A. Perez
    • , Fides D. Lay
    • , Shannon Schreiner
    • , Jiani Shi
    • , Jenevieve Polin
    •  & Peggy J. Farnham
  • Article
    | Open Access

    Three-dimensional genome organization and its effect on transcription remain elusive in rice. Here, the authors map promoter–promoter interactions and heterochromatin interactions using ChIA-PET and reveal spatial correlation between the genetic regulation of eQTLs and e-traits.

    • Lun Zhao
    • , Shuangqi Wang
    • , Zhilin Cao
    • , Weizhi Ouyang
    • , Qing Zhang
    • , Liang Xie
    • , Ruiqin Zheng
    • , Minrong Guo
    • , Meng Ma
    • , Zhe Hu
    • , Wing-Kin Sung
    • , Qifa Zhang
    • , Guoliang Li
    •  & Xingwang Li
  • Article
    | Open Access

    Compared to bulk data, cell-type-specific DNA methylation data provide higher resolution of epigenetic variation. Here, the authors introduce Tensor Composition Analysis, a novel computational approach for learning cell-type-specific DNA methylation from tissue-level bulk data, and show its application in epigenome-wide association studies.

    • Elior Rahmani
    • , Regev Schweiger
    • , Brooke Rhead
    • , Lindsey A. Criswell
    • , Lisa F. Barcellos
    • , Eleazar Eskin
    • , Saharon Rosset
    • , Sriram Sankararaman
    •  & Eran Halperin
  • Article
    | Open Access

    Plasma levels of neurological proteins have the potential to serve as biomarkers for neurological conditions. Here, Hillary et al. perform genome- and epigenome-wide association studies for 92 neurological proteins and identify 41 genomic loci for 33 proteins and 26 CpG sites for 9 proteins.

    • Robert F. Hillary
    • , Daniel L. McCartney
    • , Sarah E. Harris
    • , Anna J. Stevenson
    • , Anne Seeboth
    • , Qian Zhang
    • , David C. Liewald
    • , Kathryn L. Evans
    • , Craig W. Ritchie
    • , Elliot M. Tucker-Drob
    • , Naomi R. Wray
    • , Allan F. McRae
    • , Peter M. Visscher
    • , Ian J. Deary
    •  & Riccardo E. Marioni
  • Article
    | Open Access

    Germline cells transfer genetic information to offspring, and in zebrafish, drive sex determination. Here the authors report that, unlike mammals, the germline of zebrafish does not undergo genome-wide DNA methylation erasure, while amplifying and demethylating sex-linked rDNA during feminisation.

    • Oscar Ortega-Recalde
    • , Robert C. Day
    • , Neil J. Gemmell
    •  & Timothy A. Hore
  • Article
    | Open Access

    Germ cells are the means of transferring genetic information to the next generation. Here the authors characterise the DNA methylomes of zebrafish primordial germ cells and find that, unlike mammals, the zebrafish germ cells do not undergo genome-wide DNA demethylation but rather retain paternal DNA methylation patterns

    • Ksenia Skvortsova
    • , Katsiaryna Tarbashevich
    • , Martin Stehling
    • , Ryan Lister
    • , Manuel Irimia
    • , Erez Raz
    •  & Ozren Bogdanovic
  • Article
    | Open Access

    Spatial organization of regulatory elements and its impact on gene expression in plants remain unclear. Here, the authors construct maize chromatin interaction maps using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) and show their associations with gene expression and agronomic traits.

    • Yong Peng
    • , Dan Xiong
    • , Lun Zhao
    • , Weizhi Ouyang
    • , Shuangqi Wang
    • , Jun Sun
    • , Qing Zhang
    • , Pengpeng Guan
    • , Liang Xie
    • , Wenqiang Li
    • , Guoliang Li
    • , Jianbing Yan
    •  & Xingwang Li
  • Article
    | Open Access

    Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) can discover specific protein-centered chromatin interactions in high resolution. Here, the authors use ChIA-PET to reveal the complex and dynamic interactions between proximal and distal regulatory regions of genes in maize.

    • En Li
    • , Han Liu
    • , Liangliang Huang
    • , Xiangbo Zhang
    • , Xiaomei Dong
    • , Weibin Song
    • , Haiming Zhao
    •  & Jinsheng Lai
  • Article
    | Open Access

    Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

    • Jun Liu
    • , Elena Carnero-Montoro
    • , Jenny van Dongen
    • , Samantha Lent
    • , Ivana Nedeljkovic
    • , Symen Ligthart
    • , Pei-Chien Tsai
    • , Tiphaine C. Martin
    • , Pooja R. Mandaviya
    • , Rick Jansen
    • , Marjolein J. Peters
    • , Liesbeth Duijts
    • , Vincent W. V. Jaddoe
    • , Henning Tiemeier
    • , Janine F. Felix
    • , Gonneke Willemsen
    • , Eco J. C. de Geus
    • , Audrey Y. Chu
    • , Daniel Levy
    • , Shih-Jen Hwang
    • , Jan Bressler
    • , Rahul Gondalia
    • , Elias L. Salfati
    • , Christian Herder
    • , Bertha A. Hidalgo
    • , Toshiko Tanaka
    • , Ann Zenobia Moore
    • , Rozenn N. Lemaitre
    • , Min A Jhun
    • , Jennifer A. Smith
    • , Nona Sotoodehnia
    • , Stefania Bandinelli
    • , Luigi Ferrucci
    • , Donna K. Arnett
    • , Harald Grallert
    • , Themistocles L. Assimes
    • , Lifang Hou
    • , Andrea Baccarelli
    • , Eric A. Whitsel
    • , Ko Willems van Dijk
    • , Najaf Amin
    • , André G. Uitterlinden
    • , Eric J. G. Sijbrands
    • , Oscar H. Franco
    • , Abbas Dehghan
    • , Tim D. Spector
    • , Josée Dupuis
    • , Marie-France Hivert
    • , Jerome I. Rotter
    • , James B. Meigs
    • , James S. Pankow
    • , Joyce B. J. van Meurs
    • , Aaron Isaacs
    • , Dorret I. Boomsma
    • , Jordana T. Bell
    • , Ayşe Demirkan
    •  & Cornelia M. van Duijn
  • Article
    | Open Access

    Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

    • Darina Czamara
    • , Gökçen Eraslan
    • , Christian M. Page
    • , Jari Lahti
    • , Marius Lahti-Pulkkinen
    • , Esa Hämäläinen
    • , Eero Kajantie
    • , Hannele Laivuori
    • , Pia M. Villa
    • , Rebecca M. Reynolds
    • , Wenche Nystad
    • , Siri E. Håberg
    • , Stephanie J. London
    • , Kieran J. O’Donnell
    • , Elika Garg
    • , Michael J. Meaney
    • , Sonja Entringer
    • , Pathik D. Wadhwa
    • , Claudia Buss
    • , Meaghan J. Jones
    • , David T. S. Lin
    • , Julie L. MacIsaac
    • , Michael S. Kobor
    • , Nastassja Koen
    • , Heather J. Zar
    • , Karestan C. Koenen
    • , Shareefa Dalvie
    • , Dan J. Stein
    • , Ivan Kondofersky
    • , Nikola S. Müller
    • , Fabian J. Theis
    • , Naomi R. Wray
    • , Stephan Ripke
    • , Manuel Mattheisen
    • , Maciej Trzaskowski
    • , Enda M. Byrne
    • , Abdel Abdellaoui
    • , Mark J. Adams
    • , Esben Agerbo
    • , Tracy M. Air
    • , Till F. M. Andlauer
    • , Silviu-Alin Bacanu
    • , Marie Bækvad-Hansen
    • , Aartjan T. F. Beekman
    • , Tim B. Bigdeli
    • , Douglas H. R. Blackwood
    • , Julien Bryois
    • , Henriette N. Buttenschøn
    • , Jonas Bybjerg-Grauholm
    • , Na Cai
    • , Enrique Castelao
    • , Jane Hvarregaard Christensen
    • , Toni-Kim Clarke
    • , Jonathan R. I. Coleman
    • , Lucía Colodro-Conde
    • , Baptiste Couvy-Duchesne
    • , Nick Craddock
    • , Gregory E. Crawford
    • , Gail Davies
    • , Ian J. Deary
    • , Franziska Degenhardt
    • , Eske M. Derks
    • , Nese Direk
    • , Conor V. Dolan
    • , Erin C. Dunn
    • , Thalia C. Eley
    • , Valentina Escott-Price
    • , Farnush Farhadi Hassan Kiadeh
    • , Hilary K. Finucane
    • , Andreas J. Forstner
    • , Josef Frank
    • , Héléna A. Gaspar
    • , Michael Gill
    • , Fernando S. Goes
    • , Scott D. Gordon
    • , Jakob Grove
    • , Lynsey S. Hall
    • , Christine Søholm Hansen
    • , Thomas F. Hansen
    • , Stefan Herms
    • , Ian B. Hickie
    • , Per Hoffmann
    • , Georg Homuth
    • , Carsten Horn
    • , Jouke-Jan Hottenga
    • , David M. Hougaard
    • , Marcus Ising
    • , Rick Jansen
    • , Eric Jorgenson
    • , James A. Knowles
    • , Isaac S. Kohane
    • , Julia Kraft
    • , Warren W. Kretzschmar
    • , Jesper Krogh
    • , Zoltán Kutalik
    • , Yihan Li
    • , Penelope A. Lind
    • , Donald J. MacIntyre
    • , Dean F. MacKinnon
    • , Robert M. Maier
    • , Wolfgang Maier
    • , Jonathan Marchini
    • , Hamdi Mbarek
    • , Patrick McGrath
    • , Peter McGuffin
    • , Sarah E. Medland
    • , Divya Mehta
    • , Christel M. Middeldorp
    • , Evelin Mihailov
    • , Yuri Milaneschi
    • , Lili Milani
    • , Francis M. Mondimore
    • , Grant W. Montgomery
    • , Sara Mostafavi
    • , Niamh Mullins
    • , Matthias Nauck
    • , Bernard Ng
    • , Michel G. Nivard
    • , Dale R. Nyholt
    • , Paul F. O’Reilly
    • , Hogni Oskarsson
    • , Michael J. Owen
    • , Jodie N. Painter
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    • , Roseann E. Peterson
    • , Erik Pettersson
    • , Wouter J. Peyrot
    • , Giorgio Pistis
    • , Danielle Posthuma
    • , Jorge A. Quiroz
    • , Per Qvist
    • , John P. Rice
    • , Brien P. Riley
    • , Margarita Rivera
    • , Saira Saeed Mirza
    • , Robert Schoevers
    • , Eva C. Schulte
    • , Ling Shen
    • , Jianxin Shi
    • , Stanley I. Shyn
    • , Engilbert Sigurdsson
    • , Grant C. B. Sinnamon
    • , Johannes H. Smit
    • , Daniel J. Smith
    • , Hreinn Stefansson
    • , Stacy Steinberg
    • , Fabian Streit
    • , Jana Strohmaier
    • , Katherine E. Tansey
    • , Henning Teismann
    • , Alexander Teumer
    • , Wesley Thompson
    • , Pippa A. Thomson
    • , Thorgeir E. Thorgeirsson
    • , Matthew Traylor
    • , Jens Treutlein
    • , Vassily Trubetskoy
    • , André G. Uitterlinden
    • , Daniel Umbricht
    • , Sandra Van der Auwera
    • , Albert M. van Hemert
    • , Alexander Viktorin
    • , Peter M. Visscher
    • , Yunpeng Wang
    • , Bradley T. Webb
    • , Shantel Marie Weinsheimer
    • , Jürgen Wellmann
    • , Gonneke Willemsen
    • , Stephanie H. Witt
    • , Yang Wu
    • , Hualin S. Xi
    • , Jian Yang
    • , Futao Zhang
    • , Volker Arolt
    • , Bernhard T. Baune
    • , Klaus Berger
    • , Dorret I. Boomsma
    • , Sven Cichon
    • , Udo Dannlowski
    • , E. J. C. de Geus
    • , J. Raymond DePaulo
    • , Enrico Domenici
    • , Katharina Domschke
    • , Tõnu Esko
    • , Hans J. Grabe
    • , Steven P. Hamilton
    • , Caroline Hayward
    • , Andrew C. Heath
    • , Kenneth S. Kendler
    • , Stefan Kloiber
    • , Glyn Lewis
    • , Qingqin S. Li
    • , Susanne Lucae
    • , Pamela A. F. Madden
    • , Patrik K. Magnusson
    • , Nicholas G. Martin
    • , Andrew M. McIntosh
    • , Andres Metspalu
    • , Ole Mors
    • , Preben Bo Mortensen
    • , Bertram Müller-Myhsok
    • , Merete Nordentoft
    • , Markus M. Nöthen
    • , Michael C. O’Donovan
    • , Sara A. Paciga
    • , Nancy L. Pedersen
    • , Brenda W. J. H. Penninx
    • , Roy H. Perlis
    • , David J. Porteous
    • , James B. Potash
    • , Martin Preisig
    • , Marcella Rietschel
    • , Catherine Schaefer
    • , Thomas G. Schulze
    • , Jordan W. Smoller
    • , Kari Stefansson
    • , Henning Tiemeier
    • , Rudolf Uher
    • , Henry Völzke
    • , Myrna M. Weissman
    • , Thomas Werge
    • , Cathryn M. Lewis
    • , Douglas F. Levinson
    • , Gerome Breen
    • , Anders D. Børglum
    • , Patrick F. Sullivan
    • , Katri Räikkönen
    •  & Elisabeth B. Binder
  • Article
    | Open Access

    N6-methyladenine (6mA) DNA modification is a dynamic epigenetic mark in Drosophila embryos, but how 6mA is decoded is unclear. Here, the authors show that the protein Jumu binds 6mA-marked DNA to regulate the maternal-to-zygotic transition, partly through regulation the expression of the 6mA marked pioneer factor zelda.

    • Shunmin He
    • , Guoqiang Zhang
    • , Jiajia Wang
    • , Yajie Gao
    • , Ruidi Sun
    • , Zhijie Cao
    • , Zhenping Chen
    • , Xiudeng Zheng
    • , Jiao Yuan
    • , Yuewan Luo
    • , Xiaona Wang
    • , Wenxin Zhang
    • , Peng Zhang
    • , Yi Zhao
    • , Chuan He
    • , Yi Tao
    • , Qinmiao Sun
    •  & Dahua Chen
  • Article
    | Open Access

    Monozygotic (MZ) twins are ideal to study the influence of non-genetic factors on complex phenotypes. Here, Souren et al. perform an EWAS in peripheral blood mononuclear cells from 45 MZ twins discordant for multiple sclerosis and identify disease and treatment-associated epigenetic markers.

    • Nicole Y. Souren
    • , Lisa A. Gerdes
    • , Pavlo Lutsik
    • , Gilles Gasparoni
    • , Eduardo Beltrán
    • , Abdulrahman Salhab
    • , Tania Kümpfel
    • , Dieter Weichenhan
    • , Christoph Plass
    • , Reinhard Hohlfeld
    •  & Jörn Walter
  • Article
    | Open Access

    Risk loci for type 2 diabetes (T2D) reside in pancreatic islet enhancers. Here, the authors generate high-resolution maps of islet chromatin conformation using Hi-C which they combine with ATAC-seq and ChIP-seq data to annotate candidate target genes of enhancers and validate IGF2BP2 activity in mouse islets.

    • William W. Greenwald
    • , Joshua Chiou
    • , Jian Yan
    • , Yunjiang Qiu
    • , Ning Dai
    • , Allen Wang
    • , Naoki Nariai
    • , Anthony Aylward
    • , Jee Yun Han
    • , Nikita Kadakia
    • , Laura Regue
    • , Mei-Lin Okino
    • , Frauke Drees
    • , Dana Kramer
    • , Nicholas Vinckier
    • , Liliana Minichiello
    • , David Gorkin
    • , Joseph Avruch
    • , Kelly A. Frazer
    • , Maike Sander
    • , Bing Ren
    •  & Kyle J. Gaulton
  • Article
    | Open Access

    Dopamine dysregulation is centrally linked to major psychosis. Here, the authors characterise the hypomethylation of an enhancer within the insulin-like growth factor 2 gene in neurons of patients with major psychosis and provide evidence that this enhancer targets the tyrosine hydroxylase gene, responsible for dopamine synthesis.

    • Shraddha Pai
    • , Peipei Li
    • , Bryan Killinger
    • , Lee Marshall
    • , Peixin Jia
    • , Ji Liao
    • , Arturas Petronis
    • , Piroska E. Szabó
    •  & Viviane Labrie
  • Article
    | Open Access

    Analysis of Hi-C datasets is limited by the current existing methods for data normalization, with detection of features such as TADs and chromatin loops being inconsistent amongst different approaches. Here the authors develop Binless, a method that allows for reproducible normalization of Hi-C data independent of its resolution and compare how Binless performs in comparison with other methods.

    • Yannick G. Spill
    • , David Castillo
    • , Enrique Vidal
    •  & Marc A. Marti-Renom
  • Article
    | Open Access

    The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.

    • Huidong Chen
    • , Luca Albergante
    • , Jonathan Y. Hsu
    • , Caleb A. Lareau
    • , Giosuè Lo Bosco
    • , Jihong Guan
    • , Shuigeng Zhou
    • , Alexander N. Gorban
    • , Daniel E. Bauer
    • , Martin J. Aryee
    • , David M. Langenau
    • , Andrei Zinovyev
    • , Jason D. Buenrostro
    • , Guo-Cheng Yuan
    •  & Luca Pinello
  • Article
    | Open Access

    In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

    • Alessandro Pastore
    • , Federico Gaiti
    • , Sydney X. Lu
    • , Ryan M. Brand
    • , Scott Kulm
    • , Ronan Chaligne
    • , Hongcang Gu
    • , Kevin Y. Huang
    • , Elena K. Stamenova
    • , Wendy Béguelin
    • , Yanwen Jiang
    • , Rafael C. Schulman
    • , Kyu-Tae Kim
    • , Alicia Alonso
    • , John N. Allan
    • , Richard R. Furman
    • , Andreas Gnirke
    • , Catherine J. Wu
    • , Ari M. Melnick
    • , Alexander Meissner
    • , Bradley E. Bernstein
    • , Omar Abdel-Wahab
    •  & Dan A. Landau
  • Article
    | Open Access

    Whether plants have true DNMT3 orthologs and their role in establishing DNA methylation are still unclear. Here, the authors show that DNMT3s are persistent through plant evolution and mediates both de novo and heterochromatin DNA methylation in the early divergent land plant Physcomitrella patens.

    • Rafael Yaari
    • , Aviva Katz
    • , Katherine Domb
    • , Keith D. Harris
    • , Assaf Zemach
    •  & Nir Ohad
  • Article
    | Open Access

    In breast cancer, the 3D architecture of the genome can impact gene regulation. Here, the authors use tethered chromatin conformation profiling to investigate 3D chromatin structure in models of hormone-induced breast cancer and endocrine resistance, finding dynamic temporal reorganisation.

    • Yufan Zhou
    • , Diana L. Gerrard
    • , Junbai Wang
    • , Tian Li
    • , Yini Yang
    • , Andrew J. Fritz
    • , Mahitha Rajendran
    • , Xiaoyong Fu
    • , Rachel Schiff
    • , Shili Lin
    • , Seth Frietze
    •  & Victor X. Jin
  • Article
    | Open Access

    Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences.

    • Yanni Zeng
    • , Carmen Amador
    • , Charley Xia
    • , Riccardo Marioni
    • , Duncan Sproul
    • , Rosie M. Walker
    • , Stewart W. Morris
    • , Andrew Bretherick
    • , Oriol Canela-Xandri
    • , Thibaud S. Boutin
    • , David W. Clark
    • , Archie Campbell
    • , Konrad Rawlik
    • , Caroline Hayward
    • , Reka Nagy
    • , Albert Tenesa
    • , David J. Porteous
    • , James F. Wilson
    • , Ian J. Deary
    • , Kathryn L. Evans
    • , Andrew M. McIntosh
    • , Pau Navarro
    •  & Chris S. Haley
  • Article
    | Open Access

    Obesity and related metabolic complications represent an important health burden. Here the authors carry out a methylC-capture sequencing-based epigenome-wide association study to link circulating plasma lipid levels, CpG methylation and cardiometabolic risk across adipose and blood tissues.

    • Fiona Allum
    • , Åsa K. Hedman
    • , Xiaojian Shao
    • , Warren A. Cheung
    • , Jinchu Vijay
    • , Frédéric Guénard
    • , Tony Kwan
    • , Marie-Michelle Simon
    • , Bing Ge
    • , Cristiano Moura
    • , Elodie Boulier
    • , Lars Rönnblom
    • , Sasha Bernatsky
    • , Mark Lathrop
    • , Mark I. McCarthy
    • , Panos Deloukas
    • , André Tchernof
    • , Tomi Pastinen
    • , Marie-Claude Vohl
    •  & Elin Grundberg
  • Article
    | Open Access

    It is currently unclear how quantitative changes in chromatin loop propensity contribute to differential gene regulation. Here, the authors use phased Hi-C, RNA-seq, and ChIP-seq to show that subtle changes in loop propensity associate with differential gene regulation across cell types and haplotypes.

    • William W. Greenwald
    • , He Li
    • , Paola Benaglio
    • , David Jakubosky
    • , Hiroko Matsui
    • , Anthony Schmitt
    • , Siddarth Selvaraj
    • , Matteo D’Antonio
    • , Agnieszka D’Antonio-Chronowska
    • , Erin N. Smith
    •  & Kelly A. Frazer
  • Article
    | Open Access

    Heterogeneity in gene expression and epigenetic states exists across individual cells. Here, the authors develop scCAT-seq, a technique for simultaneously performing ATAC-seq and RNA-seq within the same single cell.

    • Longqi Liu
    • , Chuanyu Liu
    • , Andrés Quintero
    • , Liang Wu
    • , Yue Yuan
    • , Mingyue Wang
    • , Mengnan Cheng
    • , Lizhi Leng
    • , Liqin Xu
    • , Guoyi Dong
    • , Rui Li
    • , Yang Liu
    • , Xiaoyu Wei
    • , Jiangshan Xu
    • , Xiaowei Chen
    • , Haorong Lu
    • , Dongsheng Chen
    • , Quanlei Wang
    • , Qing Zhou
    • , Xinxin Lin
    • , Guibo Li
    • , Shiping Liu
    • , Qi Wang
    • , Hongru Wang
    • , J. Lynn Fink
    • , Zhengliang Gao
    • , Xin Liu
    • , Yong Hou
    • , Shida Zhu
    • , Huanming Yang
    • , Yunming Ye
    • , Ge Lin
    • , Fang Chen
    • , Carl Herrmann
    • , Roland Eils
    • , Zhouchun Shang
    •  & Xun Xu
  • Article
    | Open Access

    Transcription factors of the AP-1 family can play diverse roles despite recognizing the same DNA sequence. Here the authors investigate the DNA binding activities of AP-1 members in mouse macrophages and apply a machine learning approach to identify motifs predicted to drive factor-specific binding profiles.

    • Gregory J. Fonseca
    • , Jenhan Tao
    • , Emma M. Westin
    • , Sascha H. Duttke
    • , Nathanael J. Spann
    • , Tobias Strid
    • , Zeyang Shen
    • , Joshua D. Stender
    • , Mashito Sakai
    • , Verena M. Link
    • , Christopher Benner
    •  & Christopher K. Glass
  • Article
    | Open Access

    The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.

    • Qian Du
    • , Saul A. Bert
    • , Nicola J. Armstrong
    • , C. Elizabeth Caldon
    • , Jenny Z. Song
    • , Shalima S. Nair
    • , Cathryn M. Gould
    • , Phuc-Loi Luu
    • , Timothy Peters
    • , Amanda Khoury
    • , Wenjia Qu
    • , Elena Zotenko
    • , Clare Stirzaker
    •  & Susan J. Clark
  • Article
    | Open Access

    Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

    • Florian Haller
    • , Matthias Bieg
    • , Rainer Will
    • , Cindy Körner
    • , Dieter Weichenhan
    • , Alexander Bott
    • , Naveed Ishaque
    • , Pavlo Lutsik
    • , Evgeny A. Moskalev
    • , Sarina K. Mueller
    • , Marion Bähr
    • , Angelika Woerner
    • , Birgit Kaiser
    • , Claudia Scherl
    • , Marlen Haderlein
    • , Kortine Kleinheinz
    • , Rainer Fietkau
    • , Heinrich Iro
    • , Roland Eils
    • , Arndt Hartmann
    • , Christoph Plass
    • , Stefan Wiemann
    •  & Abbas Agaimy
  • Article
    | Open Access

    There are distinct hypermethylation patterns in gene promoters in hepatocellular carcinomas (HCCs). Here, the authors show that the enhancer of C/EBPβ is recurrently hypomethylated in human HCCs, recapitulating this in a transgenic murine model and linking aberrant enhancer hypomethylation to hepatocarcinogenesis.

    • Lei Xiong
    • , Feng Wu
    • , Qiong Wu
    • , Liangliang Xu
    • , Otto K. Cheung
    • , Wei Kang
    • , Myth T. Mok
    • , Lemuel L. M. Szeto
    • , Cheuk-Yin Lun
    • , Raymond W. Lung
    • , Jinglin Zhang
    • , Ken H. Yu
    • , Sau-Dan Lee
    • , Guangcun Huang
    • , Chiou-Miin Wang
    • , Joseph Liu
    • , Zhuo Yu
    • , Dae-Yeul Yu
    • , Jian-Liang Chou
    • , Wan-Hong Huang
    • , Bo Feng
    • , Yue-Sun Cheung
    • , Paul B. Lai
    • , Patrick Tan
    • , Nathalie Wong
    • , Michael W. Chan
    • , Tim H. Huang
    • , Kevin Y. Yip
    • , Alfred S. Cheng
    •  & Ka-Fai To
  • Article
    | Open Access

    DNA methylation is an epigenetic mark involved in gene regulation. Here the authors investigate the extent to which genetics, sex and pregnancy influence genomic DNA methylation in mice, providing evidence of the stability of CpG methylation across generation and suggest that CpG methylation may serve as an epigenetic record of life events in somatic tissues at loci whose expression is linked to the relevant biology.

    • Sara A. Grimm
    • , Takashi Shimbo
    • , Motoki Takaku
    • , James W. Thomas
    • , Scott Auerbach
    • , Brian D. Bennett
    • , John R. Bucher
    • , Adam B. Burkholder
    • , Frank Day
    • , Ying Du
    • , Christopher G. Duncan
    • , John E. French
    • , Julie F. Foley
    • , Jianying Li
    • , B. Alex Merrick
    • , Raymond R. Tice
    • , Tianyuan Wang
    • , Xiaojiang Xu
    • , Beatrice B. Barnabas
    • , Gerard G. Bouffard
    • , Shelise Y. Brooks
    • , Holly Coleman
    • , Lyudmila Dekhtyar
    • , Xiaobin Guan
    • , Joel Han
    • , Shi-ling Ho
    • , Richelle Legaspi
    • , Quino L. Maduro
    • , Catherine A. Masiello
    • , Jennifer C. McDowell
    • , Cassandra Montemayor
    • , Morgan Park
    • , Nancy L. Riebow
    • , Karen Schandler
    • , Chanthra Scharer
    • , Brian Schmidt
    • , Christina Sison
    • , Sirintorn Stantripop
    • , Pamela J. Thomas
    • , Meghana Vemulapalli
    • , Alice C. Young
    • , Pierre R. Bushel
    • , David C. Fargo
    • , James C. Mullikin
    •  & Paul A. Wade
  • Article
    | Open Access

    Transposable elements (TEs) fulfill essential but poorly understood roles in genome organization and gene expression control. Here the authors show that the regulation of TEs occurs through overlapping epigenetic mechanisms that control the expression and chromatin signatures at TEs.

    • Jiangping He
    • , Xiuling Fu
    • , Meng Zhang
    • , Fangfang He
    • , Wenjuan Li
    • , Mazid Md. Abdul
    • , Jianguo Zhou
    • , Li Sun
    • , Chen Chang
    • , Yuhao Li
    • , He Liu
    • , Kaixin Wu
    • , Isaac A. Babarinde
    • , Qiang Zhuang
    • , Yuin-Han Loh
    • , Jiekai Chen
    • , Miguel A. Esteban
    •  & Andrew P. Hutchins
  • Article
    | Open Access

    Quantification of genomic responses to environmental stimuli by current genome-scale assays is limited to indirect measurements or requires knowledge of the transcription factors involved. Here, the authors use genome-wide high-throughput reporter assays to agnostically map enhancer activity in response to glucocorticoid treatment across the human genome.

    • Graham D. Johnson
    • , Alejandro Barrera
    • , Ian C. McDowell
    • , Anthony M. D’Ippolito
    • , William H. Majoros
    • , Christopher M. Vockley
    • , Xingyan Wang
    • , Andrew S. Allen
    •  & Timothy E. Reddy
  • Article
    | Open Access

    Millions of enhancers are predicted, but their validation remains challenging. Here, the authors report genome-wide enhancer function quantification and high-resolution dissection for millions of accessible DNA fragments, revealing driver nucleotides and helping interpret non-coding disease variants.

    • Xinchen Wang
    • , Liang He
    • , Sarah M. Goggin
    • , Alham Saadat
    • , Li Wang
    • , Nasa Sinnott-Armstrong
    • , Melina Claussnitzer
    •  & Manolis Kellis
  • Article
    | Open Access

    ATAC-seq is widely used to identify regulatory regions in the genome. Here the authors develop a simple and robust plate-based single-cell ATAC-seq method that works in fresh and cryopreserved cells.

    • Xi Chen
    • , Ricardo J. Miragaia
    • , Kedar Nath Natarajan
    •  & Sarah A. Teichmann
  • Article
    | Open Access

    Copy number variants in the human genome (CNVs) are associated with neurodevelopmental and psychiatric disorders such as schizophrenia and autism. Here the authors investigate how  the large deletion CNV on chromosome 22q11.2 alters chromatin organization.

    • Xianglong Zhang
    • , Ying Zhang
    • , Xiaowei Zhu
    • , Carolin Purmann
    • , Michael S. Haney
    • , Thomas Ward
    • , Arineh Khechaduri
    • , Jie Yao
    • , Sherman M. Weissman
    •  & Alexander E. Urban
  • Article
    | Open Access

    Predicting the functional consequences of non-coding genetic variants is a challenge. Here, He et al. present GenoNet, a semi-supervised method that combines information from experimentally confirmed regulatory variants with cell type- and tissue specific annotation for function prediction.

    • Zihuai He
    • , Linxi Liu
    • , Kai Wang
    •  & Iuliana Ionita-Laza
  • Article
    | Open Access

    Mutations in genes encoding subunits of the BAF complex can cause Coffin–Siris and Nicolaides–Baraitser syndromes. Here the authors identify overlapping DNA methylation signatures in individuals with subtypes of these two syndromes that suggest a functional link and can be used to diagnose subjects with unclear clinical presentations.

    • Erfan Aref-Eshghi
    • , Eric G. Bend
    • , Rebecca L. Hood
    • , Laila C. Schenkel
    • , Deanna Alexis Carere
    • , Rana Chakrabarti
    • , Sandesh C. S. Nagamani
    • , Sau Wai Cheung
    • , Philippe M. Campeau
    • , Chitra Prasad
    • , Victoria Mok Siu
    • , Lauren Brady
    • , Mark A. Tarnopolsky
    • , David J. Callen
    • , A. Micheil Innes
    • , Susan M. White
    • , Wendy S. Meschino
    • , Andrew Y. Shuen
    • , Guillaume Paré
    • , Dennis E. Bulman
    • , Peter J. Ainsworth
    • , Hanxin Lin
    • , David I. Rodenhiser
    • , Raoul C. Hennekam
    • , Kym M. Boycott
    • , Charles E. Schwartz
    •  & Bekim Sadikovic
  • Article
    | Open Access

    Divergent transcription from promoters and enhancers occurs in many species, but it is unclear if it is a general feature of all eukaryotic cis regulatory elements. Here the authors define cis regulatory elements in worms, flies, and human; and identify several differences in regulatory architecture among metazoans.

    • Mahmoud M. Ibrahim
    • , Aslihan Karabacak
    • , Alexander Glahs
    • , Ena Kolundzic
    • , Antje Hirsekorn
    • , Alexa Carda
    • , Baris Tursun
    • , Robert P. Zinzen
    • , Scott A. Lacadie
    •  & Uwe Ohler