Global analysis of Drosophila Cys₂-His₂ zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.


:Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.


Genome Res


Genome research


Enuameh MS,Asriyan Y,Richards A,Christensen RG,Hall VL,Kazemian M,Zhu C,Pham H,Cheng Q,Blatti C,Brasefield JA,Basciotta MD,Ou J,McNulty JC,Zhu LJ,Celniker SE,Sinha S,Stormo GD,Brodsky MH,Wolfe SA




Has Abstract


2013-06-01 00:00:00














  • Ribosome profiling reveals post-transcriptional buffering of divergent gene expression in yeast.

    abstract::Understanding the patterns and causes of phenotypic divergence is a central goal in evolutionary biology. Much work has shown that mRNA abundance is highly variable between closely related species. However, the extent and mechanisms of post-transcriptional gene regulatory evolution are largely unknown. Here we used ri...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: McManus CJ,May GE,Spealman P,Shteyman A

    更新日期:2014-03-01 00:00:00

  • A periodic pattern of SNPs in the human genome.

    abstract::By surveying a filtered, high-quality set of SNPs in the human genome, we have found that SNPs positioned 1, 2, 4, 6, or 8 bp apart are more frequent than SNPs positioned 3, 5, 7, or 9 bp apart. The observed pattern is not restricted to genomic regions that are known to cause sequencing or alignment errors, for exampl...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Madsen BE,Villesen P,Wiuf C

    更新日期:2007-10-01 00:00:00

  • Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination.

    abstract::The detailed genomic organization of a gene-dense region at human chromosome 12p13, spanning 223 kb of contiguous sequence, was determined. This region is composed of 20 genes and several other expressed sequences. Experimental tools including RT-PCR and cDNA sequencing, combined with gene prediction programs, were ut...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Ansari-Lari MA,Shen Y,Muzny DM,Lee W,Gibbs RA

    更新日期:1997-03-01 00:00:00

  • Software for automated analysis of DNA fingerprinting gels.

    abstract::Here we describe software tools for the automated detection of DNA restriction fragments resolved on agarose fingerprinting gels. We present a mathematical model for the location and shape of the restriction fragments as a function of fragment size, with model parameters determined empirically from "marker" lanes cont...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Fuhrmann DR,Krzywinski MI,Chiu R,Saeedi P,Schein JE,Bosdet IE,Chinwalla A,Hillier LW,Waterston RH,McPherson JD,Jones SJ,Marra MA

    更新日期:2003-05-01 00:00:00

  • Inference of population genetic parameters in metagenomics: a clean look at messy data.

    abstract::Metagenomic projects generate short, overlapping fragments of DNA sequence, each deriving from a different individual. We report a new method for inferring the scaled mutation rate, theta = 2Neu, and the scaled exponential growth rate, R = Ner, from the site-frequency spectrum of these data while accounting for sequen...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Johnson PL,Slatkin M

    更新日期:2006-10-01 00:00:00

  • Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence.

    abstract::Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which causes Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement in OIS of chromatin reor...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Lenain C,de Graaf CA,Pagie L,Visser NL,de Haas M,de Vries SS,Peric-Hupkes D,van Steensel B,Peeper DS

    更新日期:2017-10-01 00:00:00

  • Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution.

    abstract::Low-copy repeats, or segmental duplications, are highly dynamic regions in the genome. The low-copy repeats on chromosome 22q11.2 (LCR22) are a complex mosaic of genes and pseudogenes formed by duplication processes; they mediate chromosome rearrangements associated with velo-cardio-facial syndrome/DiGeorge syndrome, ...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Babcock M,Pavlicek A,Spiteri E,Kashork CD,Ioshikhes I,Shaffer LG,Jurka J,Morrow BE

    更新日期:2003-12-01 00:00:00

  • Ride the wavelet: A multiscale analysis of genomic contexts flanking small insertions and deletions.

    abstract::Recent studies have revealed that insertions and deletions (indels) are more different in their formation than previously assumed. What remains enigmatic is how the local DNA sequence context contributes to these differences. To investigate the relative impact of various molecular mechanisms to indel formation, we ana...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kvikstad EM,Chiaromonte F,Makova KD

    更新日期:2009-07-01 00:00:00

  • An extraordinary retrotransposon family encoding dual endonucleases.

    abstract::Retrotransposons commonly encode a reverse transcriptase (RT), but other functional domains are variable. The acquisition of new domains is the dominant evolutionary force that brings structural variety to retrotransposons. Non-long-terminal-repeat (non-LTR) retrotransposons are classified into two groups by their str...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kojima KK,Fujiwara H

    更新日期:2005-08-01 00:00:00

  • A benchmark for methods in reverse engineering and model discrimination: problem formulation and solutions.

    abstract::A benchmark problem is described for the reconstruction and analysis of biochemical networks given sampled experimental data. The growth of the organisms is described in a bioreactor in which one substrate is fed into the reactor with a given feed rate and feed concentration. Measurements for some intracellular compon...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kremling A,Fischer S,Gadkar K,Doyle FJ,Sauter T,Bullinger E,Allgöwer F,Gilles ED

    更新日期:2004-09-01 00:00:00

  • Reconstructing complex regions of genomes using long-read sequencing technology.

    abstract::Obtaining high-quality sequence continuity of complex regions of recent segmental duplication remains one of the major challenges of finishing genome assemblies. In the human and mouse genomes, this was achieved by targeting large-insert clones using costly and laborious capillary-based sequencing approaches. Sanger s...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Huddleston J,Ranade S,Malig M,Antonacci F,Chaisson M,Hon L,Sudmant PH,Graves TA,Alkan C,Dennis MY,Wilson RK,Turner SW,Korlach J,Eichler EE

    更新日期:2014-04-01 00:00:00

  • An EST-enriched comparative map of Brassica oleracea and Arabidopsis thaliana.

    abstract::A detailed comparative map of Brassica oleracea and Arabidopsis thaliana has been established based largely on mapping of Arabidopsis ESTs in two Arabidopsis and four Brassica populations. Based on conservative criteria for inferring synteny, "one to one correspondence" between Brassica and Arabidopsis chromosomes acc...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Lan TH,DelMonte TA,Reischmann KP,Hyman J,Kowalski SP,McFerson J,Kresovich S,Paterson AH

    更新日期:2000-06-01 00:00:00

  • Alternative approach to a heavy weight problem.

    abstract::Obesity is reaching epidemic proportions in developed countries and represents a significant risk factor for hypertension, heart disease, diabetes, and dyslipidemia. Splicing mutations constitute at least 14% of disease-causing mutations, thus implicating polymorphisms that affect splicing as likely candidates for dis...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Goren A,Kim E,Amit M,Bochner R,Lev-Maor G,Ahituv N,Ast G

    更新日期:2008-02-01 00:00:00

  • Inferring tumor progression from genomic heterogeneity.

    abstract::Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Navin N,Krasnitz A,Rodgers L,Cook K,Meth J,Kendall J,Riggs M,Eberling Y,Troge J,Grubor V,Levy D,Lundin P,Månér S,Zetterberg A,Hicks J,Wigler M

    更新日期:2010-01-01 00:00:00

  • Profiling patterned transcripts in Drosophila embryos.

    abstract::Here we describe a high-throughput screen to isolate transcripts with spatially restricted patterns of expression in early embryos. Our approach utilizes robotic automation for rapid analysis of sequence-selected cDNAs in a whole-mount in situ hybridization assay. We determined the spatial distribution of a random col...

    journal_title:Genome research

    pub_type: 信件


    authors: Simin K,Scuderi A,Reamey J,Dunn D,Weiss R,Metherall JE,Letsou A

    更新日期:2002-07-01 00:00:00

  • Evolutionary features of the 4-Mb Xq21.3 XY homology region revealed by a map at 60-kb resolution.

    abstract::Forty-three yeast artificial chromosomes (YACs) from the X chromosome have been overlapped across the 4-Mb Xq21.3 region, which is homologous to a segment in Yp11.1. The region is formatted to 60-kb resolution with 57 STSs and is merged at its edges with contigs specific for X. This allows a direct comparison of marke...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Mumm S,Molini B,Terrell J,Srivastava A,Schlessinger D

    更新日期:1997-04-01 00:00:00

  • Long-read single-molecule maps of the functional methylome.

    abstract::We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spannin...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Sharim H,Grunwald A,Gabrieli T,Michaeli Y,Margalit S,Torchinsky D,Arielly R,Nifker G,Juhasz M,Gularek F,Almalvez M,Dufault B,Chandra SS,Liu A,Bhattacharya S,Chen YW,Vilain E,Wagner KR,Pevsner J,Reifenberger J,Lam

    更新日期:2019-04-01 00:00:00

  • Introgression maintains the genetic integrity of the mating-type determining chromosome of the fungus Neurospora tetrasperma.

    abstract::Genome evolution is driven by a complex interplay of factors, including selection, recombination, and introgression. The regions determining sexual identity are particularly dynamic parts of eukaryotic genomes that are prone to molecular degeneration associated with suppressed recombination. In the fungus Neurospora t...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Corcoran P,Anderson JL,Jacobson DJ,Sun Y,Ni P,Lascoux M,Johannesson H

    更新日期:2016-04-01 00:00:00

  • The evolution of evolvability in microRNA target sites in vertebrates.

    abstract::The lack of long-term evolutionary conservation of microRNA (miRNA) target sites appears to contradict many analyses of their functions. Several hypotheses have been offered, but an attractive one-that the conservation may be a function of taxonomic hierarchy (vertebrates, mammals, primates, etc.)-has rarely been disc...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Xu J,Zhang R,Shen Y,Liu G,Lu X,Wu CI

    更新日期:2013-11-01 00:00:00

  • Deep sequencing of tomato short RNAs identifies microRNAs targeting genes involved in fruit ripening.

    abstract::In plants there are several classes of 21-24-nt short RNAs that regulate gene expression. The most conserved class is the microRNAs (miRNAs), although some miRNAs are found only in specific species. We used high-throughput pyrosequencing to identify conserved and nonconserved miRNAs and other short RNAs in tomato frui...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Moxon S,Jing R,Szittya G,Schwach F,Rusholme Pilcher RL,Moulton V,Dalmay T

    更新日期:2008-10-01 00:00:00

  • The mRNA-bound proteome of the early fly embryo.

    abstract::Early embryogenesis is characterized by the maternal to zygotic transition (MZT), in which maternally deposited messenger RNAs are degraded while zygotic transcription begins. Before the MZT, post-transcriptional gene regulation by RNA-binding proteins (RBPs) is the dominant force in embryo patterning. We used two mRN...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Wessels HH,Imami K,Baltz AG,Kolinski M,Beldovskaya A,Selbach M,Small S,Ohler U,Landthaler M

    更新日期:2016-07-01 00:00:00

  • CRISPR RNAs trigger innate immune responses in human cells.

    abstract::Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'-ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the cytosol are recognized by DDX58, which in turn activates type I interferon r...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kim S,Koo T,Jee HG,Cho HY,Lee G,Lim DG,Shin HS,Kim JS

    更新日期:2018-02-22 00:00:00

  • DNA enrichment by allele-specific hybridization (DEASH): a novel method for haplotyping and for detecting low-frequency base substitutional variants and recombinant DNA molecules.

    abstract::Detecting rare sequence variants in genomic DNA is central to the analysis of de novo mutation and recombination events and the detection of rare pathological mutations in mixed cell populations. Current PCR techniques suffer from noise that limits detection to variants present at a frequency of at least 10(-4)-10(-5)...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Jeffreys AJ,May CA

    更新日期:2003-10-01 00:00:00

  • Natural genetic variation in C. elegans identified genomic loci controlling metabolite levels.

    abstract::Metabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium, leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitati...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Gao AW,Sterken MG,Uit de Bos J,van Creij J,Kamble R,Snoek BL,Kammenga JE,Houtkooper RH

    更新日期:2018-09-01 00:00:00

  • A genome-wide study of dual coding regions in human alternatively spliced genes.

    abstract::Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcri...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Liang H,Landweber LF

    更新日期:2006-02-01 00:00:00

  • Genomic analysis of primordial dwarfism reveals novel disease genes.

    abstract::Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in d...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Shaheen R,Faqeih E,Ansari S,Abdel-Salam G,Al-Hassnan ZN,Al-Shidi T,Alomar R,Sogaty S,Alkuraya FS

    更新日期:2014-02-01 00:00:00

  • Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently.

    abstract::Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 fro...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: David S,Rusniok C,Mentasti M,Gomez-Valero L,Harris SR,Lechat P,Lees J,Ginevra C,Glaser P,Ma L,Bouchier C,Underwood A,Jarraud S,Harrison TG,Parkhill J,Buchrieser C

    更新日期:2016-11-01 00:00:00

  • Recent segmental duplications in the working draft assembly of the brown Norway rat.

    abstract::We assessed the content, structure, and distribution of segmental duplications (> or =90% sequence identity, > or =5 kb length) within the published version of the Rattus norvegicus genome assembly (v.3.1). The overall fraction of duplicated sequence within the rat assembly (2.92%) is greater than that of the mouse (1...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Tuzun E,Bailey JA,Eichler EE

    更新日期:2004-04-01 00:00:00

  • Properties of overlapping genes are conserved across microbial genomes.

    abstract::There are numerous examples from the genomes of viruses, mitochondria, and chromosomes that adjacent genes can overlap, sharing at least one nucleotide. Overlaps have been hypothesized to be involved in genome size minimization and as a regulatory mechanism of gene expression. Here we show that overlapping genes are a...

    journal_title:Genome research

    pub_type: 信件


    authors: Johnson ZI,Chisholm SW

    更新日期:2004-11-01 00:00:00

  • Computational modeling of the Plasmodium falciparum interactome reveals protein function on a genome-wide scale.

    abstract::Many thousands of proteins encoded by the genome of Plasmodium falciparum, the causal organism of the deadliest form of human malaria, are of unknown function. It is of utmost importance that these proteins be characterized if we are to develop combative strategies against malaria based on the biology of the parasite....

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Date SV,Stoeckert CJ Jr

    更新日期:2006-04-01 00:00:00