Volume 49 Issue 6, 1 June 2017

Article

  • Article |

    William Fairbrother and colleagues use a massively parallel splicing assay (MaPSy) to analyze 4,964 exonic, disease-causing mutations for splicing defects in vivo and in vitro. They find that 10% of these exonic mutations affect splicing, and they classify these alterations by the stage of spliceosome assembly that is disrupted.

    • Rachel Soemedi
    • , Kamil J Cygan
    • , Christy L Rhine
    • , Jing Wang
    • , Charlston Bulacan
    • , John Yang
    • , Pinar Bayrak-Toydemir
    • , Jamie McDonald
    •  & William G Fairbrother
  • Article |

    John Perry, Ken Ong and colleagues analyze genotype data on 370,000 women and identify 389 independent signals that associate with age at menarche, implicating 250 genes. Their analyses suggest causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men.

    • Felix R Day
    • , Deborah J Thompson
    • , Hannes Helgason
    • , Daniel I Chasman
    • , Hilary Finucane
    • , Patrick Sulem
    • , Katherine S Ruth
    • , Sean Whalen
    • , Abhishek K Sarkar
    • , Eva Albrecht
    • , Elisabeth Altmaier
    • , Marzyeh Amini
    • , Caterina M Barbieri
    • , Thibaud Boutin
    • , Archie Campbell
    • , Ellen Demerath
    • , Ayush Giri
    • , Chunyan He
    • , Jouke J Hottenga
    • , Robert Karlsson
    • , Ivana Kolcic
    • , Po-Ru Loh
    • , Kathryn L Lunetta
    • , Massimo Mangino
    • , Brumat Marco
    • , George McMahon
    • , Sarah E Medland
    • , Ilja M Nolte
    • , Raymond Noordam
    • , Teresa Nutile
    • , Lavinia Paternoster
    • , Natalia Perjakova
    • , Eleonora Porcu
    • , Lynda M Rose
    • , Katharina E Schraut
    • , Ayellet V Segrè
    • , Albert V Smith
    • , Lisette Stolk
    • , Alexander Teumer
    • , Irene L Andrulis
    • , Stefania Bandinelli
    • , Matthias W Beckmann
    • , Javier Benitez
    • , Sven Bergmann
    • , Murielle Bochud
    • , Eric Boerwinkle
    • , Stig E Bojesen
    • , Manjeet K Bolla
    • , Judith S Brand
    • , Hiltrud Brauch
    • , Hermann Brenner
    • , Linda Broer
    • , Thomas Brüning
    • , Julie E Buring
    • , Harry Campbell
    • , Eulalia Catamo
    • , Stephen Chanock
    • , Georgia Chenevix-Trench
    • , Tanguy Corre
    • , Fergus J Couch
    • , Diana L Cousminer
    • , Angela Cox
    • , Laura Crisponi
    • , Kamila Czene
    • , George Davey Smith
    • , Eco J C N de Geus
    • , Renée de Mutsert
    • , Immaculata De Vivo
    • , Joe Dennis
    • , Peter Devilee
    • , Isabel dos-Santos-Silva
    • , Alison M Dunning
    • , Johan G Eriksson
    • , Peter A Fasching
    • , Lindsay Fernández-Rhodes
    • , Luigi Ferrucci
    • , Dieter Flesch-Janys
    • , Lude Franke
    • , Marike Gabrielson
    • , Ilaria Gandin
    • , Graham G Giles
    • , Harald Grallert
    • , Daniel F Gudbjartsson
    • , Pascal Guénel
    • , Per Hall
    • , Emily Hallberg
    • , Ute Hamann
    • , Tamara B Harris
    • , Catharina A Hartman
    • , Gerardo Heiss
    • , Maartje J Hooning
    • , John L Hopper
    • , Frank Hu
    • , David J Hunter
    • , M Arfan Ikram
    • , Hae Kyung Im
    • , Marjo-Riitta Järvelin
    • , Peter K Joshi
    • , David Karasik
    • , Manolis Kellis
    • , Zoltan Kutalik
    • , Genevieve LaChance
    • , Diether Lambrechts
    • , Claudia Langenberg
    • , Lenore J Launer
    • , Joop S E Laven
    • , Stefania Lenarduzzi
    • , Jingmei Li
    • , Penelope A Lind
    • , Sara Lindstrom
    • , YongMei Liu
    • , Jian'an Luan
    • , Reedik Mägi
    • , Arto Mannermaa
    • , Hamdi Mbarek
    • , Mark I McCarthy
    • , Christa Meisinger
    • , Thomas Meitinger
    • , Cristina Menni
    • , Andres Metspalu
    • , Kyriaki Michailidou
    • , Lili Milani
    • , Roger L Milne
    • , Grant W Montgomery
    • , Anna M Mulligan
    • , Mike A Nalls
    • , Pau Navarro
    • , Heli Nevanlinna
    • , Dale R Nyholt
    • , Albertine J Oldehinkel
    • , Tracy A O'Mara
    • , Sandosh Padmanabhan
    • , Aarno Palotie
    • , Nancy Pedersen
    • , Annette Peters
    • , Julian Peto
    • , Paul D P Pharoah
    • , Anneli Pouta
    • , Paolo Radice
    • , Iffat Rahman
    • , Susan M Ring
    • , Antonietta Robino
    • , Frits R Rosendaal
    • , Igor Rudan
    • , Rico Rueedi
    • , Daniela Ruggiero
    • , Cinzia F Sala
    • , Marjanka K Schmidt
    • , Robert A Scott
    • , Mitul Shah
    • , Rossella Sorice
    • , Melissa C Southey
    • , Ulla Sovio
    • , Meir Stampfer
    • , Maristella Steri
    • , Konstantin Strauch
    • , Toshiko Tanaka
    • , Emmi Tikkanen
    • , Nicholas J Timpson
    • , Michela Traglia
    • , Thérèse Truong
    • , Jonathan P Tyrer
    • , André G Uitterlinden
    • , Digna R Velez Edwards
    • , Veronique Vitart
    • , Uwe Völker
    • , Peter Vollenweider
    • , Qin Wang
    • , Elisabeth Widen
    • , Ko Willems van Dijk
    • , Gonneke Willemsen
    • , Robert Winqvist
    • , Bruce H R Wolffenbuttel
    • , Jing Hua Zhao
    • , Magdalena Zoledziewska
    • , Marek Zygmunt
    • , Behrooz Z Alizadeh
    • , Dorret I Boomsma
    • , Marina Ciullo
    • , Francesco Cucca
    • , Tõnu Esko
    • , Nora Franceschini
    • , Christian Gieger
    • , Vilmundur Gudnason
    • , Caroline Hayward
    • , Peter Kraft
    • , Debbie A Lawlor
    • , Patrik K E Magnusson
    • , Nicholas G Martin
    • , Dennis O Mook-Kanamori
    • , Ellen A Nohr
    • , Ozren Polasek
    • , David Porteous
    • , Alkes L Price
    • , Paul M Ridker
    • , Harold Snieder
    • , Tim D Spector
    • , Doris Stöckl
    • , Daniela Toniolo
    • , Sheila Ulivi
    • , Jenny A Visser
    • , Henry Völzke
    • , Nicholas J Wareham
    • , James F Wilson
    • , The LifeLines Cohort Study
    • , The InterAct Consortium
    • , kConFab/AOCS Investigators
    • , Endometrial Cancer Association Consortium
    • , Ovarian Cancer Association Consortium
    • , PRACTICAL consortium
    • , Amanda B Spurdle
    • , Unnur Thorsteindottir
    • , Katherine S Pollard
    • , Douglas F Easton
    • , Joyce Y Tung
    • , Jenny Chang-Claude
    • , David Hinds
    • , Anna Murray
    • , Joanne M Murabito
    • , Kari Stefansson
    • , Ken K Ong
    •  & John R B Perry

    Nature Outlook:

  • Article |

    Bradley Cairns, Douglas Carrell, Stephen Tapscott and colleagues transcriptionally profile human oocytes and preimplantation embryos and highlight DUX4-family proteins as activators of cleavage-stage genes and repetitive elements. They show that Dux expression converts mouse embryonic stem cells into two-cell (2C) embryo-like cells, thus suggesting mouse DUX and human DUX4 as drivers of the mammalian cleavage/2C state.

    • Peter G Hendrickson
    • , Jessie A Doráis
    • , Edward J Grow
    • , Jennifer L Whiddon
    • , Jong-Won Lim
    • , Candice L Wike
    • , Bradley D Weaver
    • , Christian Pflueger
    • , Benjamin R Emery
    • , Aaron L Wilcox
    • , David A Nix
    • , C Matthew Peterson
    • , Stephen J Tapscott
    • , Douglas T Carrell
    •  & Bradley R Cairns
  • Article | | open

    Jia-Xing Yue, Gianni Liti and colleagues use long-read sequencing to generate complete genome assemblies of 7 Saccharomyces cerevisiae and 5 Saccharomyces paradoxus strains. They use these data to define boundaries between chromosomal core and subtelomeric regions and to compare the evolutionary dynamics between these domesticated and wild yeast species.

    • Jia-Xing Yue
    • , Jing Li
    • , Louise Aigrain
    • , Johan Hallin
    • , Karl Persson
    • , Karen Oliver
    • , Anders Bergström
    • , Paul Coupland
    • , Jonas Warringer
    • , Marco Cosentino Lagomarsino
    • , Gilles Fischer
    • , Richard Durbin
    •  & Gianni Liti
  • Article |

    Giacomo Cavalli, Frédéric Bantignies and colleagues report the establishment of stable and isogenic Drosophila lines carrying alternative epialleles, defined by different levels of H3K27me3. They show that environmental changes modulate the expressivity of the epialleles and that epilines can be reset to a naive state, thus indicating that the inheritance of this phenotypic variability is epigenetic.

    • Filippo Ciabrelli
    • , Federico Comoglio
    • , Simon Fellous
    • , Boyan Bonev
    • , Maria Ninova
    • , Quentin Szabo
    • , Anne Xuéreb
    • , Christophe Klopp
    • , Alexei Aravin
    • , Renato Paro
    • , Frédéric Bantignies
    •  & Giacomo Cavalli
  • Article |

    Sohrab Shah, David Huntsman and colleagues report the genomic analysis of 133 ovarian cancers spanning different subtypes. They identify seven subgroups using point mutation and structural variation signatures and use these genomic features to stratify ovarian cancers both between and within histotypes.

    • Yi Kan Wang
    • , Ali Bashashati
    • , Michael S Anglesio
    • , Dawn R Cochrane
    • , Diljot S Grewal
    • , Gavin Ha
    • , Andrew McPherson
    • , Hugo M Horlings
    • , Janine Senz
    • , Leah M Prentice
    • , Anthony N Karnezis
    • , Daniel Lai
    • , Mohamed R Aniba
    • , Allen W Zhang
    • , Karey Shumansky
    • , Celia Siu
    • , Adrian Wan
    • , Melissa K McConechy
    • , Hector Li-Chang
    • , Alicia Tone
    • , Diane Provencher
    • , Manon de Ladurantaye
    • , Hubert Fleury
    • , Aikou Okamoto
    • , Satoshi Yanagida
    • , Nozomu Yanaihara
    • , Misato Saito
    • , Andrew J Mungall
    • , Richard Moore
    • , Marco A Marra
    • , C Blake Gilks
    • , Anne-Marie Mes-Masson
    • , Jessica N McAlpine
    • , Samuel Aparicio
    • , David G Huntsman
    •  & Sohrab P Shah
  • Article | | open

    Benjamin Voight and colleagues report the annotated genome of the golden orb-weaver spider. They describe 28 spider silk genes (spidroins), characterize their expression in distinct silk gland types and identify non-spidroin genes with expression patterns suggesting potential roles in silk production.

    • Paul L Babb
    • , Nicholas F Lahens
    • , Sandra M Correa-Garhwal
    • , David N Nicholson
    • , Eun Ji Kim
    • , John B Hogenesch
    • , Matjaž Kuntner
    • , Linden Higgins
    • , Cheryl Y Hayashi
    • , Ingi Agnarsson
    •  & Benjamin F Voight
  • Article |

    Michael Kharas and colleagues characterize the MSI2 protein interactome in leukemia cells and subsequently perform a functional screen identifying 24 genes required for leukemia in vivo. They focus on the RNA-binding protein SYNCRIP, showing that it regulates Hoxa9 and other transcripts involved in a myeloid leukemia stem cell program.

    • Ly P Vu
    • , Camila Prieto
    • , Elianna M Amin
    • , Sagar Chhangawala
    • , Andrei Krivtsov
    • , M Nieves Calvo-Vidal
    • , Timothy Chou
    • , Arthur Chow
    • , Gerard Minuesa
    • , Sun Mi Park
    • , Trevor S Barlowe
    • , James Taggart
    • , Patrick Tivnan
    • , Raquel P Deering
    • , Lisa P Chu
    • , Jeong-Ah Kwon
    • , Cem Meydan
    • , Javier Perales-Paton
    • , Arora Arshi
    • , Mithat Gönen
    • , Christopher Famulare
    • , Minal Patel
    • , Elisabeth Paietta
    • , Martin S Tallman
    • , Yuheng Lu
    • , Jacob Glass
    • , Francine E Garret-Bakelman
    • , Ari Melnick
    • , Ross Levine
    • , Fatima Al-Shahrour
    • , Marcus Järås
    • , Nir Hacohen
    • , Alexia Hwang
    • , Ralph Garippa
    • , Christopher J Lengner
    • , Scott A Armstrong
    • , Leandro Cerchietti
    • , Glenn S Cowley
    • , David Root
    • , John Doench
    • , Christina Leslie
    • , Benjamin L Ebert
    •  & Michael G Kharas
  • Article |

    Jonathan Cohen, Helen Hobbs and colleagues show that adiposity significantly amplifies the effects of PNPLA3, TM6SF2, and GCKR sequence variants on nonalcoholic fatty liver disease. They find that synergy between adiposity and genotype influences the full spectrum of the disease, from steatosis to hepatic inflammation and cirrhosis.

    • Stefan Stender
    • , Julia Kozlitina
    • , Børge G Nordestgaard
    • , Anne Tybjærg-Hansen
    • , Helen H Hobbs
    •  & Jonathan C Cohen
  • Article |

    Eugene Gladyshev and Nancy Kleckner report that the DNMT1-like cytosine methylase DIM-2 can mediate RIP (repeat-induced point mutation) through cytosine-to-thymine mutation of repetitive DNA in Neurospora crassa. They show that this process requires heterochromatin factors and propose a model whereby direct interactions between homologous double-stranded DNA can initiate the formation of heterochromatin.

    • Eugene Gladyshev
    •  & Nancy Kleckner
  • Article | | open

    Victor Albert, Petri Auvinen, Ykä Helariutta, Jaakko Kangasjärvi and colleagues report the reference genome of the silver birch (Betula pendula) and resequencing of 150 birch individuals. They infer past population size crashes consistent with historical periods of climatic change and identify candidate targets of more recent positive selection.

    • Jarkko Salojärvi
    • , Olli-Pekka Smolander
    • , Kaisa Nieminen
    • , Sitaram Rajaraman
    • , Omid Safronov
    • , Pezhman Safdari
    • , Airi Lamminmäki
    • , Juha Immanen
    • , Tianying Lan
    • , Jaakko Tanskanen
    • , Pasi Rastas
    • , Ali Amiryousefi
    • , Balamuralikrishna Jayaprakash
    • , Juhana I Kammonen
    • , Risto Hagqvist
    • , Gugan Eswaran
    • , Viivi Helena Ahonen
    • , Juan Alonso Serra
    • , Fred O Asiegbu
    • , Juan de Dios Barajas-Lopez
    • , Daniel Blande
    • , Olga Blokhina
    • , Tiina Blomster
    • , Suvi Broholm
    • , Mikael Brosché
    • , Fuqiang Cui
    • , Chris Dardick
    • , Sanna E Ehonen
    • , Paula Elomaa
    • , Sacha Escamez
    • , Kurt V Fagerstedt
    • , Hiroaki Fujii
    • , Adrien Gauthier
    • , Peter J Gollan
    • , Pauliina Halimaa
    • , Pekka I Heino
    • , Kristiina Himanen
    • , Courtney Hollender
    • , Saijaliisa Kangasjärvi
    • , Leila Kauppinen
    • , Colin T Kelleher
    • , Sari Kontunen-Soppela
    • , J Patrik Koskinen
    • , Andriy Kovalchuk
    • , Sirpa O Kärenlampi
    • , Anna K Kärkönen
    • , Kean-Jin Lim
    • , Johanna Leppälä
    • , Lee Macpherson
    • , Juha Mikola
    • , Katriina Mouhu
    • , Ari Pekka Mähönen
    • , Ülo Niinemets
    • , Elina Oksanen
    • , Kirk Overmyer
    • , E Tapio Palva
    • , Leila Pazouki
    • , Ville Pennanen
    • , Tuula Puhakainen
    • , Péter Poczai
    • , Boy J H M Possen
    • , Matleena Punkkinen
    • , Moona M Rahikainen
    • , Matti Rousi
    • , Raili Ruonala
    • , Christiaan van der Schoot
    • , Alexey Shapiguzov
    • , Maija Sierla
    • , Timo P Sipilä
    • , Suvi Sutela
    • , Teemu H Teeri
    • , Arja I Tervahauta
    • , Aleksia Vaattovaara
    • , Jorma Vahala
    • , Lidia Vetchinnikova
    • , Annikki Welling
    • , Michael Wrzaczek
    • , Enjun Xu
    • , Lars G Paulin
    • , Alan H Schulman
    • , Martin Lascoux
    • , Victor A Albert
    • , Petri Auvinen
    • , Ykä Helariutta
    •  & Jaakko Kangasjärvi

Letter

  • Letter |

    Kaoru Ito, Yoichiro Kamatani, Toshihiro Tanaka and colleagues report a genome-wide association study for atrial fibrillation in the Japanese population. They identify six new loci, five of which are not associated with atrial fibrillation in individuals of European ancestry, suggesting that they may be specific to the Japanese population.

    • Siew-Kee Low
    • , Atsushi Takahashi
    • , Yusuke Ebana
    • , Kouichi Ozaki
    • , Ingrid E Christophersen
    • , Patrick T Ellinor
    • , AFGen Consortium
    • , Soichi Ogishima
    • , Masayuki Yamamoto
    • , Mamoru Satoh
    • , Makoto Sasaki
    • , Taiki Yamaji
    • , Motoki Iwasaki
    • , Shoichiro Tsugane
    • , Keitaro Tanaka
    • , Mariko Naito
    • , Kenji Wakai
    • , Hideo Tanaka
    • , Tetsushi Furukawa
    • , Michiaki Kubo
    • , Kaoru Ito
    • , Yoichiro Kamatani
    •  & Toshihiro Tanaka
  • Letter |

    Patrick Ellinor and colleagues report meta-analyses of common and rare variant association studies for atrial fibrillation across multiple populations. They identify 12 new loci, some of which implicate genes in atrial electrical and mechanical function.

    • Ingrid E Christophersen
    • , Michiel Rienstra
    • , Carolina Roselli
    • , Xiaoyan Yin
    • , Bastiaan Geelhoed
    • , John Barnard
    • , Honghuang Lin
    • , Dan E Arking
    • , Albert V Smith
    • , Christine M Albert
    • , Mark Chaffin
    • , Nathan R Tucker
    • , Molong Li
    • , Derek Klarin
    • , Nathan A Bihlmeyer
    • , Siew-Kee Low
    • , Peter E Weeke
    • , Martina Müller-Nurasyid
    • , J Gustav Smith
    • , Jennifer A Brody
    • , Maartje N Niemeijer
    • , Marcus Dörr
    • , Stella Trompet
    • , Jennifer Huffman
    • , Stefan Gustafsson
    • , Claudia Schurmann
    • , Marcus E Kleber
    • , Leo-Pekka Lyytikäinen
    • , Ilkka Seppälä
    • , Rainer Malik
    • , Andrea R V R Horimoto
    • , Marco Perez
    • , Juha Sinisalo
    • , Stefanie Aeschbacher
    • , Sébastien Thériault
    • , Jie Yao
    • , Farid Radmanesh
    • , Stefan Weiss
    • , Alexander Teumer
    • , Seung Hoan Choi
    • , Lu-Chen Weng
    • , Sebastian Clauss
    • , Rajat Deo
    • , Daniel J Rader
    • , Svati H Shah
    • , Albert Sun
    • , Jemma C Hopewell
    • , Stephanie Debette
    • , Ganesh Chauhan
    • , Qiong Yang
    • , Bradford B Worrall
    • , Guillaume Paré
    • , Yoichiro Kamatani
    • , Yanick P Hagemeijer
    • , Niek Verweij
    • , Joylene E Siland
    • , Michiaki Kubo
    • , Jonathan D Smith
    • , David R Van Wagoner
    • , Joshua C Bis
    • , Siegfried Perz
    • , Bruce M Psaty
    • , Paul M Ridker
    • , Jared W Magnani
    • , Tamara B Harris
    • , Lenore J Launer
    • , M Benjamin Shoemaker
    • , Sandosh Padmanabhan
    • , Jeffrey Haessler
    • , Traci M Bartz
    • , Melanie Waldenberger
    • , Peter Lichtner
    • , Marina Arendt
    • , Jose E Krieger
    • , Mika Kähönen
    • , Lorenz Risch
    • , Alfredo J Mansur
    • , Annette Peters
    • , Blair H Smith
    • , Lars Lind
    • , Stuart A Scott
    • , Yingchang Lu
    • , Erwin B Bottinger
    • , Jussi Hernesniemi
    • , Cecilia M Lindgren
    • , Jorge A Wong
    • , Jie Huang
    • , Markku Eskola
    • , Andrew P Morris
    • , Ian Ford
    • , Alex P Reiner
    • , Graciela Delgado
    • , Lin Y Chen
    • , Yii-Der Ida Chen
    • , Roopinder K Sandhu
    • , Man Li
    • , Eric Boerwinkle
    • , Lewin Eisele
    • , Lars Lannfelt
    • , Natalia Rost
    • , Christopher D Anderson
    • , Kent D Taylor
    • , Archie Campbell
    • , Patrik K Magnusson
    • , David Porteous
    • , Lynne J Hocking
    • , Efthymia Vlachopoulou
    • , Nancy L Pedersen
    • , Kjell Nikus
    • , Marju Orho-Melander
    • , Anders Hamsten
    • , Jan Heeringa
    • , Joshua C Denny
    • , Jennifer Kriebel
    • , Dawood Darbar
    • , Christopher Newton-Cheh
    • , Christian Shaffer
    • , Peter W Macfarlane
    • , Stefanie Heilmann-Heimbach
    • , Peter Almgren
    • , Paul L Huang
    • , Nona Sotoodehnia
    • , Elsayed Z Soliman
    • , Andre G Uitterlinden
    • , Albert Hofman
    • , Oscar H Franco
    • , Uwe Völker
    • , Karl-Heinz Jöckel
    • , Moritz F Sinner
    • , Henry J Lin
    • , Xiuqing Guo
    • , METASTROKE Consortium of the ISGC
    • , Neurology Working Group of the CHARGE Consortium
    • , Martin Dichgans
    • , Erik Ingelsson
    • , Charles Kooperberg
    • , Olle Melander
    • , Ruth J F Loos
    • , Jari Laurikka
    • , David Conen
    • , Jonathan Rosand
    • , Pim van der Harst
    • , Marja-Liisa Lokki
    • , Sekar Kathiresan
    • , Alexandre Pereira
    • , J Wouter Jukema
    • , Caroline Hayward
    • , Jerome I Rotter
    • , Winfried März
    • , Terho Lehtimäki
    • , Bruno H Stricker
    • , Mina K Chung
    • , Stephan B Felix
    • , Vilmundur Gudnason
    • , Alvaro Alonso
    • , Dan M Roden
    • , Stefan Kääb
    • , Daniel I Chasman
    • , Susan R Heckbert
    • , Emelia J Benjamin
    • , Toshihiro Tanaka
    • , Kathryn L Lunetta
    • , Steven A Lubitz
    • , Patrick T Ellinor
    •  & the AFGen Consortium
  • Letter | | open

    Fei Lu, Punna Ramu and colleagues construct a cassava haplotype map (HapMapII) by using deep-sequencing data from 241 accessions and identify over 28 million segregating variants. They find that clonal propagation has led to fixation of deleterious mutations, which have been ineffectively purged, owing to limited recombination

    • Punna Ramu
    • , Williams Esuma
    • , Robert Kawuki
    • , Ismail Y Rabbi
    • , Chiedozie Egesi
    • , Jessen V Bredeson
    • , Rebecca S Bart
    • , Janu Verma
    • , Edward S Buckler
    •  & Fei Lu
  • Letter |

    Stephen Tapscott and colleagues report that human DUX4, which is linked to facioscapulohumeral dystrophy, and mouse DUX activate genes associated with cleavage-stage embryos, including retrotransposons, in muscle cells. They suggest that the ancestral DUX4-regulated genes characteristic of cleavage-stage embryos are driven by conventional promoters, whereas divergence of the DUX4 and DUX homeodomains correlates with retrotransposon specificity.

    • Jennifer L Whiddon
    • , Ashlee T Langford
    • , Chao-Jen Wong
    • , Jun Wen Zhong
    •  & Stephen J Tapscott
  • Letter |

    Didier Trono and colleagues show that both human DUX4 and mouse Dux are expressed before zygotic genome activation (ZGA) and lead to activation of ZGA-associated genes. Dux knockout in mouse embryonic stem cells prevents cycling through a 2-cell-like state, and zygotic depletion of Dux impairs embryonic development.

    • Alberto De Iaco
    • , Evarist Planet
    • , Andrea Coluccio
    • , Sonia Verp
    • , Julien Duc
    •  & Didier Trono
  • Letter |

    Igor Grigoriev and colleagues perform single-molecule real-time sequencing on 16 diverse fungal species to evaluate levels of adenine methylation (6mA). They find that almost 3% of all adenines are methylated in early-diverging fungi, and they identify clusters of methylated adenines that are enriched at transcription start sites of active genes.

    • Stephen J Mondo
    • , Richard O Dannebaum
    • , Rita C Kuo
    • , Katherine B Louie
    • , Adam J Bewick
    • , Kurt LaButti
    • , Sajeet Haridas
    • , Alan Kuo
    • , Asaf Salamov
    • , Steven R Ahrendt
    • , Rebecca Lau
    • , Benjamin P Bowen
    • , Anna Lipzen
    • , William Sullivan
    • , Bill B Andreopoulos
    • , Alicia Clum
    • , Erika Lindquist
    • , Christopher Daum
    • , Trent R Northen
    • , Govindarajan Kunde-Ramamoorthy
    • , Robert J Schmitz
    • , Andrii Gryganskyi
    • , David Culley
    • , Jon Magnuson
    • , Timothy Y James
    • , Michelle A O'Malley
    • , Jason E Stajich
    • , Joseph W Spatafora
    • , Axel Visel
    •  & Igor V Grigoriev

Analysis

  • Analysis |

    Michael Schatz, David Tuveson and colleagues analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas. They find recurrent noncoding regulatory mutations that correlate with differential expression of proximal genes and find that the strongest regulatory elements are more frequently mutated, suggesting a selective advantage for mutations in these regions.

    • Michael E Feigin
    • , Tyler Garvin
    • , Peter Bailey
    • , Nicola Waddell
    • , David K Chang
    • , David R Kelley
    • , Shimin Shuai
    • , Steven Gallinger
    • , John D McPherson
    • , Sean M Grimmond
    • , Ekta Khurana
    • , Lincoln D Stein
    • , Andrew V Biankin
    • , Michael C Schatz
    •  & David A Tuveson

Commentary

News & Views

  • News & Views |

    A DNA modification—methylation of cytosines and adenines—has important roles in diverse processes such as regulation of gene expression and genome stability, yet until recently adenine methylation had been considered to be only a hallmark of prokaryotes. A new study identifies abundant adenine methylation of transcriptionally active genes in early-diverging fungi that, together with recent other work, emphasizes the importance of adenine methylation in eukaryotes.

    • Michael F Seidl
  • News & Views |

    Three studies highlight DUX proteins as key transcription factors regulating embryonic genome activation in early mammalian development.

    • Ane Iturbide
    •  & Maria-Elena Torres-Padilla
  • News & Views |

    New work reports that both derepressed and hyper-repressed chromatin states in animals can be transmitted to progeny for many generations. Transmission depends on genomic architecture and histone modifications.

    • Vincenzo Pirrotta

Editorial

  • Editorial |

    Understanding of how epigenetic information is acquired, processed and transmitted through cell division, and potentially across generations, remains limited. Mechanistic studies aiming to elucidate the molecular underpinnings of these phenomena may provide insights into development, disease susceptibility and evolution.

Corrigendum

  • Corrigendum |

    • Clara D M van Karnebeek
    • , Luisa Bonafé
    • , Xiao-Yan Wen
    • , Maja Tarailo-Graovac
    • , Sara Balzano
    • , Beryl Royer-Bertrand
    • , Angel Ashikov
    • , Livia Garavelli
    • , Isabella Mammi
    • , Licia Turolla
    • , Catherine Breen
    • , Dian Donnai
    • , Valerie Cormier
    • , Delphine Heron
    • , Gen Nishimura
    • , Shinichi Uchikawa
    • , Belinda Campos-Xavier
    • , Antonio Rossi
    • , Thierry Hennet
    • , Koroboshka Brand-Arzamendi
    • , Jacob Rozmus
    • , Keith Harshman
    • , Brian J Stevenson
    • , Enrico Girardi
    • , Giulio Superti-Furga
    • , Tammie Dewan
    • , Alissa Collingridge
    • , Jessie Halparin
    • , Colin J Ross
    • , Margot I Van Allen
    • , Andrea Rossi
    • , Udo F Engelke
    • , Leo A J Kluijtmans
    • , Ed van der Heeft
    • , Herma Renkema
    • , Arjan de Brouwer
    • , Karin Huijben
    • , Fokje Zijlstra
    • , Thorben Heisse
    • , Thomas Boltje
    • , Wyeth W Wasserman
    • , Carlo Rivolta
    • , Sheila Unger
    • , Dirk J Lefeber
    • , Ron A Wevers
    •  & Andrea Superti-Furga
  • Corrigendum |

    • Esther Meyer
    • , Keren J Carss
    • , Julia Rankin
    • , John M E Nichols
    • , Detelina Grozeva
    • , Agnel P Joseph
    • , Niccolo E Mencacci
    • , Apostolos Papandreou
    • , Joanne Ng
    • , Serena Barral
    • , Adeline Ngoh
    • , Hilla Ben-Pazi
    • , Michel A Willemsen
    • , David Arkadir
    • , Angela Barnicoat
    • , Hagai Bergman
    • , Sanjay Bhate
    • , Amber Boys
    • , Niklas Darin
    • , Nicola Foulds
    • , Nicholas Gutowski
    • , Alison Hills
    • , Henry Houlden
    • , Jane A Hurst
    • , Zvi Israel
    • , Margaret Kaminska
    • , Patricia Limousin
    • , Daniel Lumsden
    • , Shane McKee
    • , Shibalik Misra
    • , Shekeeb S Mohammed
    • , Vasiliki Nakou
    • , Joost Nicolai
    • , Magnus Nilsson
    • , Hardev Pall
    • , Kathryn J Peall
    • , Gregory B Peters
    • , Prab Prabhakar
    • , Miriam S Reuter
    • , Patrick Rump
    • , Reeval Segel
    • , Margje Sinnema
    • , Martin Smith
    • , Peter Turnpenny
    • , Susan M White
    • , Dagmar Wieczorek
    • , Sarah Wiethoff
    • , Brian T Wilson
    • , Gidon Winter
    • , Christopher Wragg
    • , Simon Pope
    • , Simon J H Heales
    • , Deborah Morrogh
    • , UK10K Consortium
    • , Deciphering Developmental Disorders Study
    • , NIHR BioResource Rare Diseases Consortium
    • , Alan Pittman
    • , Lucinda J Carr
    • , Belen Perez-Dueñas
    • , Jean-Pierre Lin
    • , Andre Reis
    • , William A Gahl
    • , Camilo Toro
    • , Kailash P Bhatia
    • , Nicholas W Wood
    • , Erik-Jan Kamsteeg
    • , Wui K Chong
    • , Paul Gissen
    • , Maya Topf
    • , Russell C Dale
    • , Jonathan R Chubb
    • , F Lucy Raymond
    •  & Manju A Kurian
  • Corrigendum |

    • Natalie D Shaw
    • , Harrison Brand
    • , Zachary A Kupchinsky
    • , Hemant Bengani
    • , Lacey Plummer
    • , Takako I Jones
    • , Serkan Erdin
    • , Kathleen A Williamson
    • , Joe Rainger
    • , Alexei Stortchevoi
    • , Kaitlin Samocha
    • , Benjamin B Currall
    • , Donncha S Dunican
    • , Ryan L Collins
    • , Jason R Willer
    • , Angela Lek
    • , Monkol Lek
    • , Malik Nassan
    • , Shahrin Pereira
    • , Tammy Kammin
    • , Diane Lucente
    • , Alexandra Silva
    • , Catarina M Seabra
    • , Colby Chiang
    • , Yu An
    • , Morad Ansari
    • , Jacqueline K Rainger
    • , Shelagh Joss
    • , Jill Clayton Smith
    • , Margaret F Lippincott
    • , Sylvia S Singh
    • , Nirav Patel
    • , Jenny W Jing
    • , Jennifer R Law
    • , Nalton Ferraro
    • , Alain Verloes
    • , Anita Rauch
    • , Katharina Steindl
    • , Markus Zweier
    • , Ianina Scheer
    • , Daisuke Sato
    • , Nobuhiko Okamoto
    • , Christina Jacobsen
    • , Jeanie Tryggestad
    • , Steven Chernausek
    • , Lisa A Schimmenti
    • , Benjamin Brasseur
    • , Claudia Cesaretti
    • , Jose E García-Ortiz
    • , Tatiana Pineda Buitrago
    • , Orlando Perez Silva
    • , Jodi D Hoffman
    • , Wolfgang Mühlbauer
    • , Klaus W Ruprecht
    • , Bart L Loeys
    • , Masato Shino
    • , Angela M Kaindl
    • , Chie-Hee Cho
    • , Cynthia C Morton
    • , Richard R Meehan
    • , Veronica van Heyningen
    • , Eric C Liao
    • , Ravikumar Balasubramanian
    • , Janet E Hall
    • , Stephanie B Seminara
    • , Daniel Macarthur
    • , Steven A Moore
    • , Koh-ichiro Yoshiura
    • , James F Gusella
    • , Joseph A Marsh
    • , John M Graham Jr
    • , Angela E Lin
    • , Nicholas Katsanis
    • , Peter L Jones
    • , William F Crowley Jr
    • , Erica E Davis
    • , David R FitzPatrick
    •  & Michael E Talkowski
  • Corrigendum |

    • J Alberto Romero Navarro
    • , Martha Wilcox
    • , Juan Burgueño
    • , Cinta Romay
    • , Kelly Swarts
    • , Samuel Trachsel
    • , Ernesto Preciado
    • , Arturo Terron
    • , Humberto Vallejo Delgado
    • , Victor Vidal
    • , Alejandro Ortega
    • , Armando Espinoza Banda
    • , Noel Orlando Gómez Montiel
    • , Ivan Ortiz-Monasterio
    • , Félix San Vicente
    • , Armando Guadarrama Espinoza
    • , Gary Atlin
    • , Peter Wenzl
    • , Sarah Hearne
    •  & Edward S Buckler

Erratum