Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor.

Abstract:

:We present here a Sleeping Beauty-based transposition system that offers a simple and efficient way to investigate the regulatory architecture of mammalian chromosomes in vivo. With this system, we generated several hundred mice and embryos, each with a regulatory sensor inserted at a random genomic position. This large sampling of the genome revealed the widespread presence of long-range regulatory activities along chromosomes, forming overlapping blocks with distinct tissue-specific expression potentials. The presence of tissue-restricted regulatory activities around genes with widespread expression patterns challenges the gene-centric view of genome regulation and suggests that most genes are modulated in a tissue-specific manner. The local hopping property of Sleeping Beauty provides a dynamic approach to map these regulatory domains at high resolution and, combined with Cre-mediated recombination, allows for the determination of their functions by engineering mice with specific chromosomal rearrangements.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Ruf S,Symmons O,Uslu VV,Dolle D,Hot C,Ettwiller L,Spitz F

doi

10.1038/ng.790

subject

Has Abstract

pub_date

2011-03-20 00:00:00

pages

379-86

issue

4

eissn

1061-4036

issn

1546-1718

pii

ng.790

journal_volume

43

pub_type

杂志文章
  • Physical and neurobehavioral determinants of reproductive onset and success.

    abstract::The ages of puberty, first sexual intercourse and first birth signify the onset of reproductive ability, behavior and success, respectively. In a genome-wide association study of 125,667 UK Biobank participants, we identify 38 loci associated (P < 5 × 10(-8)) with age at first sexual intercourse. These findings were t...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.3551

    authors: Day FR,Helgason H,Chasman DI,Rose LM,Loh PR,Scott RA,Helgason A,Kong A,Masson G,Magnusson OT,Gudbjartsson D,Thorsteinsdottir U,Buring JE,Ridker PM,Sulem P,Stefansson K,Ong KK,Perry JRB

    更新日期:2016-06-01 00:00:00

  • A bisexually reproducing all-triploid vertebrate.

    abstract::Green toads are common in the Palaearctic region, where they have differentiated into several taxa. The toads exist with variable amounts of ploidy, similar to other anuran species or reptiles. In vertebrate biology, the very rare occurrence of triploidy is coupled with infertility or unisexuality, or requires the coe...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng839

    authors: Stöck M,Lamatsch DK,Steinlein C,Epplen JT,Grosse WR,Hock R,Klapperstück T,Lampert KP,Scheer U,Schmid M,Schartl M

    更新日期:2002-03-01 00:00:00

  • Distinct in vivo requirements for establishment versus maintenance of transcriptional repression.

    abstract::Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashio...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng942

    authors: Wheeler JC,VanderZwan C,Xu X,Swantek D,Tracey WD,Gergen JP

    更新日期:2002-09-01 00:00:00

  • Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.

    abstract::Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in severa...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng994

    authors: Xu J,Zheng SL,Komiya A,Mychaleckyj JC,Isaacs SD,Hu JJ,Sterling D,Lange EM,Hawkins GA,Turner A,Ewing CM,Faith DA,Johnson JR,Suzuki H,Bujnovszky P,Wiley KE,DeMarzo AM,Bova GS,Chang B,Hall MC,McCullough DL,Partin A

    更新日期:2002-10-01 00:00:00

  • Canalization of development by microRNAs.

    abstract::Animal development is an extremely robust process resulting in stereotyped outcomes. Canalization is a design principle wherein developmental pathways are stabilized to increase phenotypic reproducibility. Recent revelations into microRNA (miRNA) function suggest that miRNAs act as key players in canalizing genetic pr...

    journal_title:Nature genetics

    pub_type: 杂志文章,评审

    doi:10.1038/ng1803

    authors: Hornstein E,Shomron N

    更新日期:2006-06-01 00:00:00

  • Meristems take their cues from organ primordia.

    abstract::Stem cell regulation is critical to the development of all multicellular organisms; in plants, stem cell niches reside in meristems. Two newly identified plant genes establish a novel signaling feedback from the incipient leaf primordia back to the meristem that is required to regulate stem cell proliferation. ...

    journal_title:Nature genetics

    pub_type: 评论,杂志文章

    doi:10.1038/ng.3601

    authors: Strable J,Scanlon MJ

    更新日期:2016-06-28 00:00:00

  • Lineage-specific functions of TET1 in the postimplantation mouse embryo.

    abstract::The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation st...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.3868

    authors: Khoueiry R,Sohni A,Thienpont B,Luo X,Velde JV,Bartoccetti M,Boeckx B,Zwijsen A,Rao A,Lambrechts D,Koh KP

    更新日期:2017-07-01 00:00:00

  • Molecular portraits and the family tree of cancer.

    abstract::The twenty-first century heralds a new era for the biological sciences and medicine. The tools of our time are allowing us to analyze complex genomes more comprehensively than ever before. A principal technology contributing to this explosion of information is the DNA microarray, which enables us to study genome-wide ...

    journal_title:Nature genetics

    pub_type: 杂志文章,评审

    doi:10.1038/ng1038

    authors: Chung CH,Bernard PS,Perou CM

    更新日期:2002-12-01 00:00:00

  • Direct detection of novel expanded trinucleotide repeats in the human genome.

    abstract::Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two-step cycling process that ...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng0693-135

    authors: Schalling M,Hudson TJ,Buetow KH,Housman DE

    更新日期:1993-06-01 00:00:00

  • Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53.

    abstract::The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a critical regulator of tumorigenesis. This protein is negatively regulated by a physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo in a p5...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng714

    authors: Parant J,Chavez-Reyes A,Little NA,Yan W,Reinke V,Jochemsen AG,Lozano G

    更新日期:2001-09-01 00:00:00

  • Ancestry estimation and control of population stratification for sequence-based association studies.

    abstract::Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysi...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.2924

    authors: Wang C,Zhan X,Bragg-Gresham J,Kang HM,Stambolian D,Chew EY,Branham KE,Heckenlively J,FUSION Study.,Fulton R,Wilson RK,Mardis ER,Lin X,Swaroop A,Zöllner S,Abecasis GR

    更新日期:2014-04-01 00:00:00

  • A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans.

    abstract::The fundamental aim of genetics is to understand how an organism's phenotype is determined by its genotype, and implicit in this is predicting how changes in DNA sequence alter phenotypes. A single network covering all the genes of an organism might guide such predictions down to the level of individual cells and tiss...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.2007.70

    authors: Lee I,Lehner B,Crombie C,Wong W,Fraser AG,Marcotte EM

    更新日期:2008-02-01 00:00:00

  • A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma.

    abstract::The molecular mechanisms underlying angioimmunoblastic T cell lymphoma (AITL), a common type of mature T cell lymphoma of poor prognosis, are largely unknown. Here we report a frequent somatic mutation in RHOA (encoding p.Gly17Val) using exome and transcriptome sequencing of samples from individuals with AITL. Further...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.2916

    authors: Yoo HY,Sung MK,Lee SH,Kim S,Lee H,Park S,Kim SC,Lee B,Rho K,Lee JE,Cho KH,Kim W,Ju H,Kim J,Kim SJ,Kim WS,Lee S,Ko YH

    更新日期:2014-04-01 00:00:00

  • Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome.

    abstract::Crouzon syndrome is an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis) and maps to chromosome 10q25-q26. We now present evidence that mutations in the fibroblast growth factor receptor 2 gene (FGFR2) cause Crouzon syndrome. We found SSCP variations in the B exon of FGFR2...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng0994-98

    authors: Reardon W,Winter RM,Rutland P,Pulleyn LJ,Jones BM,Malcolm S

    更新日期:1994-09-01 00:00:00

  • Promoter bivalency favors an open chromatin architecture in embryonic stem cells.

    abstract::In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genom...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/s41588-018-0218-5

    authors: Mas G,Blanco E,Ballaré C,Sansó M,Spill YG,Hu D,Aoi Y,Le Dily F,Shilatifard A,Marti-Renom MA,Di Croce L

    更新日期:2018-10-01 00:00:00

  • Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture.

    abstract::Manipulation or non-physiological embryo culture environments can lead to defective fetal programming in livestock. Our demonstration of reduced fetal methylation and expression of ovine IGF2R suggests pre-implantation embryo procedures may be vulnerable to epigenetic alterations in imprinted genes. This highlights th...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/84769

    authors: Young LE,Fernandes K,McEvoy TG,Butterwith SC,Gutierrez CG,Carolan C,Broadbent PJ,Robinson JJ,Wilmut I,Sinclair KD

    更新日期:2001-02-01 00:00:00

  • Mekk3 is essential for early embryonic cardiovascular development.

    abstract::The early development of blood vessels consists of two phases, vasculogenesis and angiogenesis, which involve distinct and also overlapping molecular regulators, but the intracellular signal transduction pathways involved in these processes have not been well defined. We disrupted Map3k3 (also known as Mekk3), which e...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/73550

    authors: Yang J,Boerm M,McCarty M,Bucana C,Fidler IJ,Zhuang Y,Su B

    更新日期:2000-03-01 00:00:00

  • Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome.

    abstract::The approach to annotating a genome critically affects the number and accuracy of genes identified in the genome sequence. Genome annotation based on stringent gene identification is prone to underestimate the complement of genes encoded in a genome. In contrast, over-prediction of putative genes followed by exhaustiv...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/85922

    authors: Gopal S,Schroeder M,Pieper U,Sczyrba A,Aytekin-Kurban G,Bekiranov S,Fajardo JE,Eswar N,Sanchez R,Sali A,Gaasterland T

    更新日期:2001-03-01 00:00:00

  • Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia).

    abstract::Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. Electromyographic investigations reveal repetitive m...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/82638

    authors: Nicole S,Davoine CS,Topaloglu H,Cattolico L,Barral D,Beighton P,Hamida CB,Hammouda H,Cruaud C,White PS,Samson D,Urtizberea JA,Lehmann-Horn F,Weissenbach J,Hentati F,Fontaine B

    更新日期:2000-12-01 00:00:00

  • Exome sequencing of liver fluke-associated cholangiocarcinoma.

    abstract::Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes us...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.2273

    authors: Ong CK,Subimerb C,Pairojkul C,Wongkham S,Cutcutache I,Yu W,McPherson JR,Allen GE,Ng CC,Wong BH,Myint SS,Rajasegaran V,Heng HL,Gan A,Zang ZJ,Wu Y,Wu J,Lee MH,Huang D,Ong P,Chan-on W,Cao Y,Qian CN,Lim KH,Ooi

    更新日期:2012-05-06 00:00:00

  • Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans.

    abstract::More than 5 million single-nucleotide polymorphisms (SNPs) with minor-allele frequency greater than 10% are expected to exist in the human genome. Some of these SNPs may be associated with risk of developing common diseases. To assess the power of currently available SNPs to detect such associations, we resequenced 50...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng1128

    authors: Carlson CS,Eberle MA,Rieder MJ,Smith JD,Kruglyak L,Nickerson DA

    更新日期:2003-04-01 00:00:00

  • Haplotype-resolved genome analyses of a heterozygous diploid potato.

    abstract::Potato (Solanum tuberosum L.) is the most important tuber crop worldwide. Efforts are underway to transform the crop from a clonally propagated tetraploid into a seed-propagated, inbred-line-based hybrid, but this process requires a better understanding of potato genome. Here, we report the 1.67-Gb haplotype-resolved ...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/s41588-020-0699-x

    authors: Zhou Q,Tang D,Huang W,Yang Z,Zhang Y,Hamilton JP,Visser RGF,Bachem CWB,Robin Buell C,Zhang Z,Zhang C,Huang S

    更新日期:2020-10-01 00:00:00

  • Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions.

    abstract::We introduce new statistical methods for analyzing genomic data sets that measure many effects in many conditions (for example, gene expression changes under many treatments). These new methods improve on existing methods by allowing for arbitrary correlations in effect sizes among conditions. This flexible approach i...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/s41588-018-0268-8

    authors: Urbut SM,Wang G,Carbonetto P,Stephens M

    更新日期:2019-01-01 00:00:00

  • Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.

    abstract::Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increas...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.731

    authors: Painter JN,Anderson CA,Nyholt DR,Macgregor S,Lin J,Lee SH,Lambert A,Zhao ZZ,Roseman F,Guo Q,Gordon SD,Wallace L,Henders AK,Visscher PM,Kraft P,Martin NG,Morris AP,Treloar SA,Kennedy SH,Missmer SA,Montgomery GW,Z

    更新日期:2011-01-01 00:00:00

  • The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits.

    abstract::Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The pla...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.2604

    authors: Schartl M,Walter RB,Shen Y,Garcia T,Catchen J,Amores A,Braasch I,Chalopin D,Volff JN,Lesch KP,Bisazza A,Minx P,Hillier L,Wilson RK,Fuerstenberg S,Boore J,Searle S,Postlethwait JH,Warren WC

    更新日期:2013-05-01 00:00:00

  • Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis.

    abstract::It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by sear...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng1294-380

    authors: Houwen RH,Baharloo S,Blankenship K,Raeymaekers P,Juyn J,Sandkuijl LA,Freimer NB

    更新日期:1994-12-01 00:00:00

  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    abstract::Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 ad...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.686

    authors: Speliotes EK,Willer CJ,Berndt SI,Monda KL,Thorleifsson G,Jackson AU,Lango Allen H,Lindgren CM,Luan J,Mägi R,Randall JC,Vedantam S,Winkler TW,Qi L,Workalemahu T,Heid IM,Steinthorsdottir V,Stringham HM,Weedon MN,Wheel

    更新日期:2010-11-01 00:00:00

  • Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains.

    abstract::Congenic breeding strategies are becoming increasingly important as a greater number of complex trait linkages are identified. Traditionally, the development of a congenic strain has been a time-consuming endeavour, requiring ten generations of backcrosses. The recent advent of a dense molecular genetic map of the mou...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng1197-280

    authors: Markel P,Shu P,Ebeling C,Carlson GA,Nagle DL,Smutko JS,Moore KJ

    更新日期:1997-11-01 00:00:00

  • Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution.

    abstract::Human endogenous retroviruses (HERVs), which are remnants of past retroviral infections of the germline cells of our ancestors, make up as much as 8% of the human genome and may even outnumber genes. Most HERVs seem to have entered the genome between 10 and 50 million years ago, and they comprise over 200 distinct gro...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng775

    authors: Hughes JF,Coffin JM

    更新日期:2001-12-01 00:00:00

  • Genetic interactions improve models of quantitative traits.

    abstract::A study of genetic variation in yeast has identified key quantitative trait loci (QTLs) that suppress the effects of variation at multiple other loci. These loci prove essential to accurately modeling yeast growth in response to different environments. ...

    journal_title:Nature genetics

    pub_type: 杂志文章

    doi:10.1038/ng.3829

    authors: Tyler AL,Carter GW

    更新日期:2017-03-30 00:00:00