Volume 43 Issue 7, July 2011

Volume 43 Issue 7

Cover art: Fabric of Life Series – Ecological Symmetries Charaxes anticlea DMPR1X1 by John Arabolos http://arabolosart.com/

Editorial

  • Editorial |

    Our first Nature Conference in China emphasized the value of extending genome-wide association studies (GWAS) to populations worldwide as a way to promote cooperation and high standards in research while gaining a wealth of biological insights into common and complex diseases and traits.

News and Views

  • News & Views |

    Large-scale mapping of chromatin state and transcription factor binding have uncovered many broad chromatin domains along linear genomic DNA, but it is unclear how these functional domains are organized in three-dimensional nuclear space. A new study now shows that many domains exist as loops connected by CCTC-binding factor (CTCF), providing new insights into the higher-order structure of chromatin organization in the nucleus.

    • Celso A Espinoza
    •  & Bing Ren
  • News & Views |

    Transcription of genomic loci containing protein-coding genes often yields not only cognate mRNAs but also assorted noncoding RNAs (ncRNAs), which typically map in the vicinity of transcription start sites. A new study shows that far from being random byproducts of gene expression, many long ncRNAs (lncRNAs) are synthesized in a coordinate fashion and control important cellular processes, such as survival in the face of DNA damage.

    • Elena Sotillo
    •  & Andrei Thomas-Tikhonenko
  • News & Views |

    Although there are only 22,000 human genes, most express multiple mRNA isoforms through alternative splicing and selection of alternative 5′ and 3′ ends. A new study identifies the role of alternative splicing in maintaining neuronal excitability in the adult mouse brain.

    • Thomas A Cooper

Research Highlights

Articles

  • Article |

    David Wong, Howard Chang and colleagues report the identification of long noncoding RNAs transcribed from the promoters of cell-cycle genes. Many of these RNAs have periodic expression during the cell-cycle and are regulated by oncogenic stimuli, stem cell differentiation or DNA damage.

    • Tiffany Hung
    • , Yulei Wang
    • , Michael F Lin
    • , Ashley K Koegel
    • , Yojiro Kotake
    • , Gavin D Grant
    • , Hugo M Horlings
    • , Nilay Shah
    • , Christopher Umbricht
    • , Pei Wang
    • , Yu Wang
    • , Benjamin Kong
    • , Anita Langerød
    • , Anne-Lise Børresen-Dale
    • , Seung K Kim
    • , Marc van de Vijver
    • , Saraswati Sukumar
    • , Michael L Whitfield
    • , Manolis Kellis
    • , Yue Xiong
    • , David J Wong
    •  & Howard Y Chang
  • Article |

    Chia-Lin Wei, Yijun Ruan and colleagues used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to determine the CTCF-chromatin interactome in mouse embryonic stem cells.

    • Lusy Handoko
    • , Han Xu
    • , Guoliang Li
    • , Chew Yee Ngan
    • , Elaine Chew
    • , Marie Schnapp
    • , Charlie Wah Heng Lee
    • , Chaopeng Ye
    • , Joanne Lim Hui Ping
    • , Fabianus Mulawadi
    • , Eleanor Wong
    • , Jianpeng Sheng
    • , Yubo Zhang
    • , Thompson Poh
    • , Chee Seng Chan
    • , Galih Kunarso
    • , Atif Shahab
    • , Guillaume Bourque
    • , Valere Cacheux-Rataboul
    • , Wing-Kin Sung
    • , Yijun Ruan
    •  & Chia-Lin Wei
  • Article |

    Stefan Somlo and colleagues show that the polycystic liver disease genes Prkcsh and Sec63 are required for the proper biogenesis of polycystin complexes. They further show that a Pkd1 transgene can rescue the cystic phenotype of Prkcsh and Sec63 mutant mice, identifying polycystin-1 as the central determinant of cyst formation.

    • Sorin V Fedeles
    • , Xin Tian
    • , Anna-Rachel Gallagher
    • , Michihiro Mitobe
    • , Saori Nishio
    • , Seung Hun Lee
    • , Yiqiang Cai
    • , Lin Geng
    • , Craig M Crews
    •  & Stefan Somlo
  • Article |

    Fernando Pardo-Manuel de Villena, Gary Churchill and colleagues provide a high-resolution phylogenetic map of mouse inbred strains based on comparisons to wild-caught mice. They show that the genomes of classical strains are overwhelmingly derived from Mus musculus domesticus whereas wild-derived laboratory strains include a broad sampling of diversity from multiple subspecies with pervasive introgression. The subspecific origin, haplotype diversity and identity-by-descent map of laboratory strains can be visualized at http://msub.csbio.unc.edu/PhylogenyTool.html.

    • Hyuna Yang
    • , Jeremy R Wang
    • , John P Didion
    • , Ryan J Buus
    • , Timothy A Bell
    • , Catherine E Welsh
    • , François Bonhomme
    • , Alex Hon-Tsen Yu
    • , Michael W Nachman
    • , Jaroslav Pialek
    • , Priscilla Tucker
    • , Pierre Boursot
    • , Leonard McMillan
    • , Gary A Churchill
    •  & Fernando Pardo-Manuel de Villena
  • Article |

    Balázs Papp and colleagues construct a genetic interaction map of yeast metabolism and use a genome-scale systems biology model to examine the structure of the metabolic network. They use an automated machine-learning method to reconcile differences between the experimental and computational genetic interaction maps. In contrast to previous studies, they do not find evidence for prevalent positive interactions in essential metabolic genes.

    • Balázs Szappanos
    • , Károly Kovács
    • , Béla Szamecz
    • , Frantisek Honti
    • , Michael Costanzo
    • , Anastasia Baryshnikova
    • , Gabriel Gelius-Dietrich
    • , Martin J Lercher
    • , Márk Jelasity
    • , Chad L Myers
    • , Brenda J Andrews
    • , Charles Boone
    • , Stephen G Oliver
    • , Csaba Pál
    •  & Balázs Papp

Letters

  • Letter |

    Alberto Cascón, Mercedes Robledo and colleagues show that MAX germline mutations confer susceptibility to hereditary pheochromocytoma. This finding supports a key role for MAX and its interaction partners in tumors of neural crest cell origin.

    • Iñaki Comino-Méndez
    • , Francisco J Gracia-Aznárez
    • , Francesca Schiavi
    • , Iñigo Landa
    • , Luis J Leandro-García
    • , Rocío Letón
    • , Emiliano Honrado
    • , Rocío Ramos-Medina
    • , Daniela Caronia
    • , Guillermo Pita
    • , Álvaro Gómez-Graña
    • , Aguirre A de Cubas
    • , Lucía Inglada-Pérez
    • , Agnieszka Maliszewska
    • , Elisa Taschin
    • , Sara Bobisse
    • , Giuseppe Pica
    • , Paola Loli
    • , Rafael Hernández-Lavado
    • , José A Díaz
    • , Mercedes Gómez-Morales
    • , Anna González-Neira
    • , Giovanna Roncador
    • , Cristina Rodríguez-Antona
    • , Javier Benítez
    • , Massimo Mannelli
    • , Giuseppe Opocher
    • , Mercedes Robledo
    •  & Alberto Cascón
  • Letter |

    Marc Ladanyi and colleagues show that the nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma (MPM). They further show that knockdown of BAP1 in MPM cell lines affects E2F and Polycomb target genes, implicating transcriptional deregulation in disease pathogenesis.

    • Matthew Bott
    • , Marie Brevet
    • , Barry S Taylor
    • , Shigeki Shimizu
    • , Tatsuo Ito
    • , Lu Wang
    • , Jenette Creaney
    • , Richard A Lake
    • , Maureen F Zakowski
    • , Boris Reva
    • , Chris Sander
    • , Robert Delsite
    • , Simon Powell
    • , Qin Zhou
    • , Ronglai Shen
    • , Adam Olshen
    • , Valerie Rusch
    •  & Marc Ladanyi
  • Letter |

    Hans-Guido Wendel and colleagues identify five miRNAs that are capable of promoting T-ALL in a mouse model and that account for the majority of miRNA expression in human T-ALL. They show that these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL.

    • Konstantinos J Mavrakis
    • , Joni Van Der Meulen
    • , Andrew L Wolfe
    • , Xiaoping Liu
    • , Evelien Mets
    • , Tom Taghon
    • , Aly A Khan
    • , Manu Setty
    • , Pieter Rondou
    • , Peter Vandenberghe
    • , Eric Delabesse
    • , Yves Benoit
    • , Nicholas B Socci
    • , Christina S Leslie
    • , Pieter Van Vlierberghe
    • , Frank Speleman
    •  & Hans-Guido Wendel
  • Letter |

    Dongxin Lin and colleagues report a genome-wide association study for esophageal squamous-cell carcinoma in Chinese populations. They identify three new susceptibility loci at 5q11, 6p21 and 21q22.

    • Chen Wu
    • , Zhibin Hu
    • , Zhonghu He
    • , Weihua Jia
    • , Feng Wang
    • , Yifeng Zhou
    • , Zhihua Liu
    • , Qimin Zhan
    • , Yu Liu
    • , Dianke Yu
    • , Kan Zhai
    • , Jiang Chang
    • , Yan Qiao
    • , Guangfu Jin
    • , Zhe Liu
    • , Yuanyuan Shen
    • , Chuanhai Guo
    • , Jianhua Fu
    • , Xiaoping Miao
    • , Wen Tan
    • , Hongbing Shen
    • , Yang Ke
    • , Yixin Zeng
    • , Tangchun Wu
    •  & Dongxin Lin
  • Letter |

    Omar Albagha, Stuart Ralston and colleagues report the identification of three new loci associated with risk for Paget's disease of bone.

    • the Genetic Determinants of Paget's Disease (GDPD) Consortium
    • , Omar M E Albagha
    • , Sachin E Wani
    • , Micaela R Visconti
    • , Nerea Alonso
    • , Kirsteen Goodman
    • , Maria Luisa Brandi
    • , Tim Cundy
    • , Pui Yan Jenny Chung
    • , Rosemary Dargie
    • , Jean-Pierre Devogelaer
    • , Alberto Falchetti
    • , William D Fraser
    • , Luigi Gennari
    • , Fernando Gianfrancesco
    • , Michael J Hooper
    • , Wim Van Hul
    • , Gianluca Isaia
    • , Geoff C Nicholson
    • , Ranuccio Nuti
    • , Socrates Papapoulos
    • , Javier del Pino Montes
    • , Thomas Ratajczak
    • , Sarah L Rea
    • , Domenico Rendina
    • , Rogelio Gonzalez-Sarmiento
    • , Marco Di Stefano
    • , Lynley C Ward
    • , John P Walsh
    •  & Stuart H Ralston
  • Letter |

    Xue-Jun Zhang, Zhi-Rong Yao and colleagues report a genome-wide association study for atopic dermatitis in the Chinese Han population. They identified two new susceptibility loci at 5q22 and 20q13.

    • Liang-Dan Sun
    • , Feng-Li Xiao
    • , Yang Li
    • , Wen-Ming Zhou
    • , Hua-Yang Tang
    • , Xian-Fa Tang
    • , Hui Zhang
    • , Heidi Schaarschmidt
    • , Xian-Bo Zuo
    • , Regina Foelster-Holst
    • , Su-Min He
    • , Mei Shi
    • , Qiang Liu
    • , Yong-Mei Lv
    • , Xi-Lan Chen
    • , Kun-Ju Zhu
    • , Yi-Feng Guo
    • , Da-Yan Hu
    • , Ming Li
    • , Min Li
    • , Yan-Hong Zhang
    • , Xin Zhang
    • , Jian-Ping Tang
    • , Bi-Rong Guo
    • , Hua Wang
    • , Yuan Liu
    • , Xiao-Yan Zou
    • , Fu-Sheng Zhou
    • , Xiao-Yan Liu
    • , Gang Chen
    • , Lin Ma
    • , Shu-Mei Zhang
    • , Ai-Ping Jiang
    • , Xiao-Dong Zheng
    • , Xing-Hua Gao
    • , Pan Li
    • , Cai-Xia Tu
    • , Xian-Yong Yin
    • , Xiu-Ping Han
    • , Yun-Qing Ren
    • , Shun-Peng Song
    • , Zhi-Yong Lu
    • , Xing-Lian Zhang
    • , Yong Cui
    • , Jing Chang
    • , Min Gao
    • , Xiao-Yan Luo
    • , Pei-Guang Wang
    • , Xing Dai
    • , Wei Su
    • , Hui Li
    • , Chun-Pin Shen
    • , Sheng-Xiu Liu
    • , Xiao-Bo Feng
    • , Chun-Jun Yang
    • , Guo-Shu Lin
    • , Zai-Xing Wang
    • , Jian-Qing Huang
    • , Xing Fan
    • , Yan Wang
    • , Yi-Xiao Bao
    • , Sen Yang
    • , Jian-Jun Liu
    • , Andre Franke
    • , Stephan Weidinger
    • , Zhi-Rong Yao
    •  & Xue-Jun Zhang
  • Letter |

    Markus Schürks and colleagues report a genome-wide association study for common migraine. They identify three new susceptibility loci at PRDM16, TRPM8 and LRP1.

    • Daniel I Chasman
    • , Markus Schürks
    • , Verneri Anttila
    • , Boukje de Vries
    • , Ulf Schminke
    • , Lenore J Launer
    • , Gisela M Terwindt
    • , Arn M J M van den Maagdenberg
    • , Konstanze Fendrich
    • , Henry Völzke
    • , Florian Ernst
    • , Lyn R Griffiths
    • , Julie E Buring
    • , Mikko Kallela
    • , Tobias Freilinger
    • , Christian Kubisch
    • , Paul M Ridker
    • , Aarno Palotie
    • , Michel D Ferrari
    • , Wolfgang Hoffmann
    • , Robert Y L Zee
    •  & Tobias Kurth
  • Letter |

    Gerard Schellenberg and colleagues report a genome-wide association study for progressive supranuclear palsy, a movement disorder with prominent tau neuropathology. They identified three new risk loci and confirmed the known risk locus at MAPT.

    • Günter U Höglinger
    • , Nadine M Melhem
    • , Dennis W Dickson
    • , Patrick M A Sleiman
    • , Li-San Wang
    • , Lambertus Klei
    • , Rosa Rademakers
    • , Rohan de Silva
    • , Irene Litvan
    • , David E Riley
    • , John C van Swieten
    • , Peter Heutink
    • , Zbigniew K Wszolek
    • , Ryan J Uitti
    • , Jana Vandrovcova
    • , Howard I Hurtig
    • , Rachel G Gross
    • , Walter Maetzler
    • , Stefano Goldwurm
    • , Eduardo Tolosa
    • , Barbara Borroni
    • , Pau Pastor
    • , PSP Genetics Study Group
    • , Roger L Albin
    • , Elena Alonso
    • , Angelo Antonini
    • , Manuela Apfelbacher
    • , Steven E Arnold
    • , Jesus Avila
    • , Thomas G Beach
    • , Sherry Beecher
    • , Daniela Berg
    • , Thomas D Bird
    • , Nenad Bogdanovic
    • , Agnita J W Boon
    • , Yvette Bordelon
    • , Alexis Brice
    • , Herbert Budka
    • , Margherita Canesi
    • , Wang Zheng Chiu
    • , Roberto Cilia
    • , Carlo Colosimo
    • , Peter P De Deyn
    • , Justo García de Yebenes
    • , Laura Donker Kaat
    • , Ranjan Duara
    • , Alexandra Durr
    • , Sebastiaan Engelborghs
    • , Giovanni Fabbrini
    • , NiCole A Finch
    • , Robyn Flook
    • , Matthew P Frosch
    • , Carles Gaig
    • , Douglas R Galasko
    • , Thomas Gasser
    • , Marla Gearing
    • , Evan T Geller
    • , Bernardino Ghetti
    • , Neill R Graff-Radford
    • , Murray Grossman
    • , Deborah A Hall
    • , Lili-Naz Hazrati
    • , Matthias Höllerhage
    • , Joseph Jankovic
    • , Jorge L Juncos
    • , Anna Karydas
    • , Hans A Kretzschmar
    • , Isabelle Leber
    • , Virginia M Lee
    • , Andrew P Lieberman
    • , Kelly E Lyons
    • , Claudio Mariani
    • , Eliezer Masliah
    • , Luke A Massey
    • , Catriona A McLean
    • , Nicoletta Meucci
    • , Bruce L Miller
    • , Brit Mollenhauer
    • , Jens C Möller
    • , Huw R Morris
    • , Chris Morris
    • , Sean S O'Sullivan
    • , Wolfgang H Oertel
    • , Donatella Ottaviani
    • , Alessandro Padovani
    • , Rajesh Pahwa
    • , Gianni Pezzoli
    • , Stuart Pickering-Brown
    • , Werner Poewe
    • , Alberto Rabano
    • , Alex Rajput
    • , Stephen G Reich
    • , Gesine Respondek
    • , Sigrun Roeber
    • , Jonathan D Rohrer
    • , Owen A Ross
    • , Martin N Rossor
    • , Giorgio Sacilotto
    • , William W Seeley
    • , Klaus Seppi
    • , Laura Silveira-Moriyama
    • , Salvatore Spina
    • , Karin Srulijes
    • , Peter St. George-Hyslop
    • , Maria Stamelou
    • , David G Standaert
    • , Silvana Tesei
    • , Wallace W Tourtellotte
    • , Claudia Trenkwalder
    • , Claire Troakes
    • , John Q Trojanowski
    • , Juan C Troncoso
    • , Vivianna M Van Deerlin
    • , Jean Paul G Vonsattel
    • , Gregor K Wenning
    • , Charles L White
    • , Pia Winter
    • , Chris Zarow
    • , Anna L Zecchinelli
    • , Laura B Cantwell
    • , Mi Ryung Han
    • , Allissa Dillman
    • , Marcel P van der Brug
    • , J Raphael Gibbs
    • , Mark R Cookson
    • , Dena G Hernandez
    • , Andrew B Singleton
    • , Matthew J Farrer
    • , Chang-En Yu
    • , Lawrence I Golbe
    • , Tamas Revesz
    • , John Hardy
    • , Andrew J Lees
    • , Bernie Devlin
    • , Hakon Hakonarson
    • , Ulrich Müller
    •  & Gerard D Schellenberg
  • Letter |

    The Rbfox family of RNA binding proteins mediate alternative splicing. Douglas Black and colleagues show that targeted deletion of the mouse Rbfox1 gene in the CNS alters splice isoforms of a subset of genes and is associated with neural hyperexcitability with spontaneous and drug-induced seizures.

    • Lauren T Gehman
    • , Peter Stoilov
    • , Jamie Maguire
    • , Andrey Damianov
    • , Chia-Ho Lin
    • , Lily Shiue
    • , Manuel Ares Jr
    • , Istvan Mody
    •  & Douglas L Black
  • Letter |

    Matthew Hurles and colleagues report the first direct comparative analysis of male and female germline mutation rates from whole-genome sequences of two parent-offspring trios sequenced as part of the 1000 Genomes Project. They identify variation in paternal and maternal mutation rates between these two families.

    • the 1000 Genomes Project
    • , Donald F Conrad
    • , Jonathan E M Keebler
    • , Mark A DePristo
    • , Sarah J Lindsay
    • , Yujun Zhang
    • , Ferran Casals
    • , Youssef Idaghdour
    • , Chris L Hartl
    • , Carlos Torroja
    • , Kiran V Garimella
    • , Martine Zilversmit
    • , Reed Cartwright
    • , Guy A Rouleau
    • , Mark Daly
    • , Eric A Stone
    • , Matthew E Hurles
    •  & Philip Awadalla
  • Letter |

    Xiaofeng Cao and colleagues report that REF6 is a histone H3 lysine 27 demethylase in Arabidopsis. REF6 demethylates H3K27me3 and H3K27me2 and ref6 mutant plants resemble mutations in H3K27me3-mediated gene silencing.

    • Falong Lu
    • , Xia Cui
    • , Shuaibin Zhang
    • , Thomas Jenuwein
    •  & Xiaofeng Cao

Corrigendum

  • Corrigendum |

    • Patrick Tarpey
    • , Shery Thomas
    • , Nagini Sarvananthan
    • , Uma Mallya
    • , Steven Lisgo
    • , Chris J Talbot
    • , Eryl O Roberts
    • , Musarat Awan
    • , Mylvaganam Surendran
    • , Rebecca J McLean
    • , Robert D Reinecke
    • , Andrea Langmann
    • , Susanne Lindner
    • , Martina Koch
    • , Sunila Jain
    • , Geoffrey Woodruff
    • , Richard P Gale
    • , Chris Degg
    • , Konstantinos Droutsas
    • , Ioannis Asproudis
    • , Alina A Zubcov
    • , Christina Pieh
    • , Colin D Veal
    • , Rajiv D Machado
    • , Oliver C Backhouse
    • , Laura Baumber
    • , Cris S Constantinescu
    • , Michael C Brodsky
    • , David G Hunter
    • , Richard W Hertle
    • , Randy J Read
    • , Sarah Edkins
    • , Sarah O'Meara
    • , Adrian Parker
    • , Claire Stevens
    • , Jon Teague
    • , Richard Wooster
    • , P Andrew Futreal
    • , Richard C Trembath
    • , Michael R Stratton
    • , F Lucy Raymond
    •  & Irene Gottlob