Browse Articles

  • Article |

    The authors report that DNA methylation coevolves with the DNA alkylation repair enzyme ALKB2 across eukaryotes. They also show that DNA methyltransferases cause alkylation damage in vitro and in vivo by introducing 3-methylcytosine into DNA.

    • Silvana Rošić
    • , Rachel Amouroux
    • , Cristina E. Requena
    • , Ana Gomes
    • , Max Emperle
    • , Toni Beltran
    • , Jayant K. Rane
    • , Sarah Linnett
    • , Murray E. Selkirk
    • , Philipp H. Schiffer
    • , Allison J. Bancroft
    • , Richard K. Grencis
    • , Albert Jeltsch
    • , Petra Hajkova
    •  & Peter Sarkies
  • Article |

    The authors report a data-driven approach to phenotyping 3D facial shape. They apply their methodology to 2,329 individuals of European ancestry and identify 38 loci that associate with specific facial morphologies, some of which overlap with neural-crest-specific regulatory regions.

    • Peter Claes
    • , Jasmien Roosenboom
    • , Julie D. White
    • , Tomek Swigut
    • , Dzemila Sero
    • , Jiarui Li
    • , Myoung Keun Lee
    • , Arslan Zaidi
    • , Brooke C. Mattern
    • , Corey Liebowitz
    • , Laurel Pearson
    • , Tomás González
    • , Elizabeth J. Leslie
    • , Jenna C. Carlson
    • , Ekaterina Orlova
    • , Paul Suetens
    • , Dirk Vandermeulen
    • , Eleanor Feingold
    • , Mary L. Marazita
    • , John R. Shaffer
    • , Joanna Wysocka
    • , Mark D. Shriver
    •  & Seth M. Weinberg
  • Article |

    The authors find that, in a high-fat diet (HFD) mouse model, levels of Stella protein are reduced in oocytes, leading to abnormal epigenetic patterning during development and to embryonic growth defects. Overexpression of Stella in oocytes from HFD-fed mice partially ameliorates developmental defects.

    • Longsen Han
    • , Chao Ren
    • , Ling Li
    • , Xiaoyan Li
    • , Juan Ge
    • , Haichao Wang
    • , Yi-Liang Miao
    • , Xuejiang Guo
    • , Kelle H. Moley
    • , Qiang Wang
    •  & Wenjie Shu
  • Letter |

    Meta-analysis of data from 58,265 cattle shows that the genetic architecture underlying stature is similar to that in humans, where many genomic regions individually explain only a small amount of phenotypic variance.

    • Aniek C. Bouwman
    • , Hans D. Daetwyler
    • , Amanda J. Chamberlain
    • , Carla Hurtado Ponce
    • , Mehdi Sargolzaei
    • , Flavio S. Schenkel
    • , Goutam Sahana
    • , Armelle Govignon-Gion
    • , Simon Boitard
    • , Marlies Dolezal
    • , Hubert Pausch
    • , Rasmus F. Brøndum
    • , Phil J. Bowman
    • , Bo Thomsen
    • , Bernt Guldbrandtsen
    • , Mogens S. Lund
    • , Bertrand Servin
    • , Dorian J. Garrick
    • , James Reecy
    • , Johanna Vilkki
    • , Alessandro Bagnato
    • , Min Wang
    • , Jesse L. Hoff
    • , Robert D. Schnabel
    • , Jeremy F. Taylor
    • , Anna A. E. Vinkhuyzen
    • , Frank Panitz
    • , Christian Bendixen
    • , Lars-Erik Holm
    • , Birgit Gredler
    • , Chris Hozé
    • , Mekki Boussaha
    • , Marie-Pierre Sanchez
    • , Dominique Rocha
    • , Aurelien Capitan
    • , Thierry Tribout
    • , Anne Barbat
    • , Pascal Croiseau
    • , Cord Drögemüller
    • , Vidhya Jagannathan
    • , Christy Vander Jagt
    • , John J. Crowley
    • , Anna Bieber
    • , Deirdre C. Purfield
    • , Donagh P. Berry
    • , Reiner Emmerling
    • , Kay-Uwe Götz
    • , Mirjam Frischknecht
    • , Ingolf Russ
    • , Johann Sölkner
    • , Curtis P. Van Tassell
    • , Ruedi Fries
    • , Paul Stothard
    • , Roel F. Veerkamp
    • , Didier Boichard
    • , Mike E. Goddard
    •  & Ben J. Hayes
  • Letter |

    Identification of AvrStb6, the fungal avirulence effector that triggers Stb6-mediated resistance in wheat, here demonstrates that neither host resistance nor fungicide treatment suppresses fungal sexual reproduction, thus unveiling implications of fungal sex in plant disease control.

    • Gerrit H. J. Kema
    • , Amir Mirzadi Gohari
    • , Lamia Aouini
    • , Hesham A. Y. Gibriel
    • , Sarah B. Ware
    • , Frank van den Bosch
    • , Robbie Manning-Smith
    • , Vasthi Alonso-Chavez
    • , Joe Helps
    • , Sarrah Ben M’Barek
    • , Rahim Mehrabi
    • , Caucasella Diaz-Trujillo
    • , Elham Zamani
    • , Henk J. Schouten
    • , Theo A. J. van der Lee
    • , Cees Waalwijk
    • , Maarten A. de Waard
    • , Pierre J. G. M. de Wit
    • , Els C. P. Verstappen
    • , Bart P. H. J. Thomma
    • , Harold J. G. Meijer
    •  & Michael F. Seidl
  • Letter |

    The authors report map-based cloning of the wheat Stb6 gene, which encodes a conserved wall-associated receptor kinase (WAK)-like protein. Stb6 confers gene-for-gene disease resistance to fungal pathogen Zymoseptoria tritici by recognition of a matching pathogen effector.

    • Cyrille Saintenac
    • , Wing-Sham Lee
    • , Florence Cambon
    • , Jason J. Rudd
    • , Robert C. King
    • , William Marande
    • , Stephen J. Powers
    • , Hélène Bergès
    • , Andy L. Phillips
    • , Cristobal Uauy
    • , Kim E. Hammond-Kosack
    • , Thierry Langin
    •  & Kostya Kanyuka
  • Letter |

    Whole-exome sequencing identifies mutations in CLCN2 in individuals with familial hyperaldosteronism type II or early-onset primary aldosteronism. These gain-of-function mutations cause chloride channel opening and glomerulosa cell depolarization, showing a role for anion channels in aldosterone production.

    • Ute I. Scholl
    • , Gabriel Stölting
    • , Julia Schewe
    • , Anne Thiel
    • , Hua Tan
    • , Carol Nelson-Williams
    • , Alfred A. Vichot
    • , Sheng Chih Jin
    • , Erin Loring
    • , Verena Untiet
    • , Taekyeong Yoo
    • , Jungmin Choi
    • , Shengxin Xu
    • , Aihua Wu
    • , Marieluise Kirchner
    • , Philipp Mertins
    • , Lars C. Rump
    • , Ali Mirza Onder
    • , Cory Gamble
    • , Daniel McKenney
    • , Robert W. Lash
    • , Deborah P. Jones
    • , Gary Chune
    • , Priscila Gagliardi
    • , Murim Choi
    • , Richard Gordon
    • , Michael Stowasser
    • , Christoph Fahlke
    •  & Richard P. Lifton
  • Letter |

    A gain-of-function mutation in the CLCN2 chloride channel gene (encoding ClC-2) causes primary aldosteronism. The mutation abolishes voltage-dependent gating of ClC-2, highlighting a role for chloride conduction in regulating aldosterone biosynthesis.

    • Fabio L. Fernandes-Rosa
    • , Georgios Daniil
    • , Ian J. Orozco
    • , Corinna Göppner
    • , Rami El Zein
    • , Vandana Jain
    • , Sheerazed Boulkroun
    • , Xavier Jeunemaitre
    • , Laurence Amar
    • , Hervé Lefebvre
    • , Thomas Schwarzmayr
    • , Tim M. Strom
    • , Thomas J. Jentsch
    •  & Maria-Christina Zennaro
  • Article |

    A genome-wide association study (GWAS) of 58 traits using data from the Biobank Japan Project identifies 1,407 loci, 679 of which are novel. Comparison with disease GWASs and analysis of genetic correlations and cell-type enrichment show that these clinical measurements are relevant to human disease.

    • Masahiro Kanai
    • , Masato Akiyama
    • , Atsushi Takahashi
    • , Nana Matoba
    • , Yukihide Momozawa
    • , Masashi Ikeda
    • , Nakao Iwata
    • , Shiro Ikegawa
    • , Makoto Hirata
    • , Koichi Matsuda
    • , Michiaki Kubo
    • , Yukinori Okada
    •  & Yoichiro Kamatani
  • Letter |

    Exome-wide analyses identify low-frequency coding variants associated with esophageal squamous cell carcinoma. One of the risk variants, in CYP26B1, is associated with enhanced enzymatic activity and lower levels of all-trans retinoic acid in serum.

    • Jiang Chang
    • , Rong Zhong
    • , Jianbo Tian
    • , Jiaoyuan Li
    • , Kan Zhai
    • , Juntao Ke
    • , Jiao Lou
    • , Wei Chen
    • , Beibei Zhu
    • , Na Shen
    • , Yi Zhang
    • , Ying Zhu
    • , Yajie Gong
    • , Yang Yang
    • , Danyi Zou
    • , Xiating Peng
    • , Zhi Zhang
    • , Xuemei Zhang
    • , Kun Huang
    • , Tangchun Wu
    • , Chen Wu
    • , Xiaoping Miao
    •  & Dongxin Lin
  • Brief Communication |

    The clinical phenotype associated with BRD4 haploinsufficiency overlaps with Cornelia de Lange syndrome, which is often caused by mutations in NIPBL. The authors show that BRD4 and NIPBL physically interact and co-bind at super-enhancers.

    • Gabrielle Olley
    • , Morad Ansari
    • , Hemant Bengani
    • , Graeme R. Grimes
    • , James Rhodes
    • , Alex von Kriegsheim
    • , Ana Blatnik
    • , Fiona J. Stewart
    • , Emma Wakeling
    • , Nicola Carroll
    • , Alison Ross
    • , Soo-Mi Park
    • , Wendy A. Bickmore
    • , Madapura M. Pradeepa
    •  & David R. FitzPatrick
  • Article |

    Analysis of chromatin accessibility and expression quantitative trait loci in stimulated or naïve macrophages identifies loci that constitutively alter chromatin but affect expression only after stimulation, thus indicating an effect on enhancer priming.

    • Kaur Alasoo
    • , Julia Rodrigues
    • , Subhankar Mukhopadhyay
    • , Andrew J. Knights
    • , Alice L. Mann
    • , Kousik Kundu
    • , Christine Hale
    • , Gordon Dougan
    •  & Daniel J. Gaffney
  • Article |

    This study investigates the effects of MYCN on the chromatin and transcriptional landscape of neuroblastoma. The authors find that, at oncogenic levels, MYCN binds to canonical E-boxes at promoters and invades enhancers, leading to transcriptional amplification.

    • Rhamy Zeid
    • , Matthew A. Lawlor
    • , Evon Poon
    • , Jaime M. Reyes
    • , Mariateresa Fulciniti
    • , Michael A. Lopez
    • , Thomas G. Scott
    • , Behnam Nabet
    • , Michael A. Erb
    • , Georg E. Winter
    • , Zoe Jacobson
    • , Donald R. Polaski
    • , Kristen L. Karlin
    • , Rachel A. Hirsch
    • , Nikhil P. Munshi
    • , Thomas F. Westbrook
    • , Louis Chesler
    • , Charles Y. Lin
    •  & James E. Bradner
  • Editorial |

    The reconstruction of the genome of a woman of African ancestry from her European descendants, across eight generations, connects living people to a documented saga, drawing attention to the individuals who participated in historic events at a time when the legal, cultural and ethical implications of individual human rights began to gain currency. It is also a technical achievement that extends the methodologies for understanding our interwoven genomic and social histories.

  • News & Views |

    New genomic analyses indicate that pioneer transcription factors can sample a diverse repertoire of common binding sites among different cell types and become enriched where they cooperate with other factors specific to each cell. Pioneer-factor binding is mechanistically separate from, and is necessary for, subsequent phenomena of chromatin opening and epigenetic memory in vivo.

    • Kenneth S. Zaret
  • News & Views |

    Two new studies identify rare homozygous variants in ADCY3 that are causal for monogenic obesity in consanguineous families of Pakistani origin and are associated with increased risk of obesity in Greenlandic individuals. Greenlandic carriers of homozygous loss-of-function variants in ADCY3, and individuals from trans-ancestry studies with a burden of rare ADCY3 loss-of-function variants, also have increased risk of type 2 diabetes.

    • Inês Barroso
  • Article |

    Investigation of FOXA2, GATA4 and OCT4 binding across several cell types provides insights into the genetic determinants and epigenetic effects of pioneer-factor occupancy. The data suggest that FOXA2 samples most of its potential binding sites but is stabilized at only a subset of targets.

    • Julie Donaghey
    • , Sudhir Thakurela
    • , Jocelyn Charlton
    • , Jennifer S. Chen
    • , Zachary D. Smith
    • , Hongcang Gu
    • , Ramona Pop
    • , Kendell Clement
    • , Elena K. Stamenova
    • , Rahul Karnik
    • , David R. Kelley
    • , Casey A. Gifford
    • , Davide Cacchiarelli
    • , John L. Rinn
    • , Andreas Gnirke
    • , Michael J. Ziller
    •  & Alexander Meissner
  • Article |

    The study reports map-based cloning and functional analysis of Bph6, which is associated with resistance to planthoppers in rice. BPH6 localizes to the exocyst and interacts with OsEXO70E1, and suppression of OsExo70E1 expression decreases resistance in Bph6-NIL plants.

    • Jianping Guo
    • , Chunxue Xu
    • , Di Wu
    • , Yan Zhao
    • , Yongfu Qiu
    • , Xiaoxiao Wang
    • , Yidan Ouyang
    • , Baodong Cai
    • , Xin Liu
    • , Shengli Jing
    • , Xinxin Shangguan
    • , Huiying Wang
    • , Yinhua Ma
    • , Liang Hu
    • , Yan Wu
    • , Shaojie Shi
    • , Wenliang Wang
    • , Lili Zhu
    • , Xun Xu
    • , Rongzhi Chen
    • , Yuqi Feng
    • , Bo Du
    •  & Guangcun He
  • Article |

    Analysis of Pax7 dynamics during pituitary lineage specification shows that Pax7 binds rapidly at uniquely marked heterochromatin pioneer sites and initiates chromatin opening that remains stable after Pax7 withdrawal, with loss of DNA hypermethylation at pioneered enhancers.

    • Alexandre Mayran
    • , Konstantin Khetchoumian
    • , Fadi Hariri
    • , Tomi Pastinen
    • , Yves Gauthier
    • , Aurelio Balsalobre
    •  & Jacques Drouin
  • Article | | open

    Genome assemblies of 13 domesticated and wild rice relatives reveal salient features of genome evolution across the genus Oryza, especially rapid species diversification and turnover of transposons. This study also releases a complete long-read assembly of IR 8 ‘Miracle Rice’.

    • Joshua C. Stein
    • , Yeisoo Yu
    • , Dario Copetti
    • , Derrick J. Zwickl
    • , Li Zhang
    • , Chengjun Zhang
    • , Kapeel Chougule
    • , Dongying Gao
    • , Aiko Iwata
    • , Jose Luis Goicoechea
    • , Sharon Wei
    • , Jun Wang
    • , Yi Liao
    • , Muhua Wang
    • , Julie Jacquemin
    • , Claude Becker
    • , Dave Kudrna
    • , Jianwei Zhang
    • , Carlos E. M. Londono
    • , Xiang Song
    • , Seunghee Lee
    • , Paul Sanchez
    • , Andrea Zuccolo
    • , Jetty S. S. Ammiraju
    • , Jayson Talag
    • , Ann Danowitz
    • , Luis F. Rivera
    • , Andrea R. Gschwend
    • , Christos Noutsos
    • , Cheng-chieh Wu
    • , Shu-min Kao
    • , Jhih-wun Zeng
    • , Fu-jin Wei
    • , Qiang Zhao
    • , Qi Feng
    • , Moaine El Baidouri
    • , Marie-Christine Carpentier
    • , Eric Lasserre
    • , Richard Cooke
    • , Daniel da Rosa Farias
    • , Luciano Carlos da Maia
    • , Railson S. dos Santos
    • , Kevin G. Nyberg
    • , Kenneth L. McNally
    • , Ramil Mauleon
    • , Nickolai Alexandrov
    • , Jeremy Schmutz
    • , Dave Flowers
    • , Chuanzhu Fan
    • , Detlef Weigel
    • , Kshirod K. Jena
    • , Thomas Wicker
    • , Mingsheng Chen
    • , Bin Han
    • , Robert Henry
    • , Yue-ie C. Hsing
    • , Nori Kurata
    • , Antonio Costa de Oliveira
    • , Olivier Panaud
    • , Scott A. Jackson
    • , Carlos A. Machado
    • , Michael J. Sanderson
    • , Manyuan Long
    • , Doreen Ware
    •  & Rod A. Wing
  • Article |

    A GWAS of multi- and extensively drug-resistant tuberculosis using 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries identifies novel mutations associated with resistance. The capacity to detect resistance in particular to ethionamide, pyrazinamide, capreomycin, cycloserine and paraaminosalicylic acid was enhanced by inclusion of insertions and deletions.

    • Francesc Coll
    • , Jody Phelan
    • , Grant A. Hill-Cawthorne
    • , Mridul B. Nair
    • , Kim Mallard
    • , Shahjahan Ali
    • , Abdallah M. Abdallah
    • , Saad Alghamdi
    • , Mona Alsomali
    • , Abdallah O. Ahmed
    • , Stephanie Portelli
    • , Yaa Oppong
    • , Adriana Alves
    • , Theolis Barbosa Bessa
    • , Susana Campino
    • , Maxine Caws
    • , Anirvan Chatterjee
    • , Amelia C. Crampin
    • , Keertan Dheda
    • , Nicholas Furnham
    • , Judith R. Glynn
    • , Louis Grandjean
    • , Dang Minh Ha
    • , Rumina Hasan
    • , Zahra Hasan
    • , Martin L. Hibberd
    • , Moses Joloba
    • , Edward C. Jones-López
    • , Tomoshige Matsumoto
    • , Anabela Miranda
    • , David J. Moore
    • , Nora Mocillo
    • , Stefan Panaiotov
    • , Julian Parkhill
    • , Carlos Penha
    • , João Perdigão
    • , Isabel Portugal
    • , Zineb Rchiad
    • , Jaime Robledo
    • , Patricia Sheen
    • , Nashwa Talaat Shesha
    • , Frik A. Sirgel
    • , Christophe Sola
    • , Erivelton Oliveira Sousa
    • , Elizabeth M. Streicher
    • , Paul Van Helden
    • , Miguel Viveiros
    • , Robert M. Warren
    • , Ruth McNerney
    • , Arnab Pain
    •  & Taane G. Clark
  • Article | | open

    A new assembly of the sea lamprey germline genome identifies genomic regions that are systematically eliminated from somatic tissue during early development. Comparative analysis gives new insight into vertebrate evolution.

    • Jeramiah J. Smith
    • , Nataliya Timoshevskaya
    • , Chengxi Ye
    • , Carson Holt
    • , Melissa C. Keinath
    • , Hugo J. Parker
    • , Malcolm E. Cook
    • , Jon E. Hess
    • , Shawn R. Narum
    • , Francesco Lamanna
    • , Henrik Kaessmann
    • , Vladimir A. Timoshevskiy
    • , Courtney K. M. Waterbury
    • , Cody Saraceno
    • , Leanne M. Wiedemann
    • , Sofia M. C. Robb
    • , Carl Baker
    • , Evan E. Eichler
    • , Dorit Hockman
    • , Tatjana Sauka-Spengler
    • , Mark Yandell
    • , Robb Krumlauf
    • , Greg Elgar
    •  & Chris T. Amemiya