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Plos Genetics : Aging and Environmental Exposures Alter Tissue-spe...

By: Dirk Schubeler

Description : Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are relat...

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Plos Genetics : Identification of Genes Required for Neural-specif...

By: Norbert Perrimon

Description : Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, a1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific a1,3-fucosylation is regulated. In the present study, we searched for genes involved in the glycosylation of a ne...

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Plos Genetics : Gene-based Tests of Association, Volume 7

By: Mark I. McCarthy

Description : Genome-wide association studies (GWAS) are now used routinely to identify SNPs associated with complex human phenotypes. In several cases, multiple variants within a gene contribute independently to disease risk. Here we introduce a novel Gene-Wide Significance (GWiS) test that uses greedy Bayesian model selection to identify the independent effects within a gene, which are combined to generate a stronger statistical signal. Permutation tests provide p-valu...

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Plos Genetics : Rest–mediated Recruitment of Polycomb Repressor Co...

By: Hiten D. Madhani

Description : Polycomb Repressive Complex (PRC) 1 and PRC2 regulate genes involved in differentiation and development. However, the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear. Here we present evidence for an interaction between the transcription factor REST, PRC1, and PRC2 and show that RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma cells (NT2-D1). Using NT2-D1 cells as a model of neuronal different...

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Plos Genetics : Comparative Analysis of the Genomes of Two Field I...

By: Paul M. Richardson

Description : Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice worldwide. The fungal pathogen is notorious for its ability to overcome host resistance. To better understand its genetic variation in nature, we sequenced the genomes of two field isolates, Y34 and P131. In comparison with the previously sequenced laboratory strain 70-15, both field isolates had a similar genome size but slightly more genes. Sequences from the field iso...

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Plos Genetics : a Closer Look at the Evestripe 2 Enhancers of Dros...

By: Norbert Perrimon

Description : Gene regulatory sequences have been investigated and/or proposed to be important targets of natural selection during animal evolution [1–14]. However, much controversy has been generated by the contention that they are not likely to be as important as functional protein-coding evolution given the low number of such examples established to date [15,16]. However, an important obstacle in identifying such sequences is our lack of understanding of the organizat...

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Plos Genetics : Genetic Requirements for Signaling from an Autoact...

By: John M. McDowell

Description : Plants react to pathogen attack via recognition of, and response to, pathogen-specific molecules at the cell surface and inside the cell. Pathogen effectors (virulence factors) are monitored by intracellular nucleotide-binding leucine-rich repeat (NB-LRR) sensor proteins in plants and mammals. Here, we study the genetic requirements for defense responses of an autoactive mutant of ADR1-L2, an Arabidopsis coiled-coil (CC)-NB-LRR protein. ADR1-L2 functions up...

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Plos Genetics : Induction of Cytoprotective Pathways is Central to...

By: Stuart K. Kim

Description : Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 ge...

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Plos Genetics : Inter-homolog Crossing-over and Synapsis in Arabid...

By: R. Scott Hawley

Description : In this study we have analysed AtASY3, a coiled-coil domain protein that is required for normal meiosis in Arabidopsis. Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers (COs). Although the frequency of DNA double-strand breaks (DSBs) appears moderately reduced in Atasy3-1, the main recombination defect is a reduction in the formation of COs. Immunolocal...

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Plos Genetics : Dynamic Switch of Negative Feedback Regulation in ...

By: Gregory S. Barsh

Description : Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism. The activity of Akt must be carefully balanced, as increased Akt signaling is frequently associated with cancer and as insufficient Akt signaling is linked to metabolic disease and diabetes mellitus. Using a genome-wide RNAi screen in Drosophila cells in culture, and in vivo analyses in th...

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Plos Genetics : Mu Insertions Are Repaired by the Double-strand Br...

By: Diarmaid Hughes

Description : Mu is both a transposable element and a temperate bacteriophage. During lytic growth, it amplifies its genome by replicative transposition. During infection, it integrates into the Escherichia coli chromosome through a mechanism not requiring extensive DNA replication. In the latter pathway, the transposition intermediate is repaired by transposasemediated resecting of the 59 flaps attached to the ends of the incoming Mu genome, followed by filling the rema...

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Plos Genetics : the Evolution of Spinnable Cotton Fiber Entailed P...

By: Ken Olsen

Description : A central question in evolutionary biology concerns the developmental processes by which new phenotypes arise. An exceptional example of evolutionary innovation is the single-celled seed trichome in Gossypium (‘‘cotton fiber’’). We have used fiber development in Gossypium as a system to understand how morphology can rapidly evolve. Fiber has undergone considerable morphological changes between the short, tightly adherent fibers of G. longicalyx and the deri...

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Plos Genetics : Mi2Β is Required for Γ-globin Gene Silencing ; Tem...

By: Gregory S. Barsh

Description : Activation of c-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same : an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the 2566 GATA motif of the Ac-globin gene. We show that Mi2b is essential for c-globin gene silencing using Mi2b ...

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Plos Genetics : an African Ancestry-specific Allele of Ctla4Confer...

By: Jonathan Marchini

Description : Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ,1.0%: RA is purportedly less common in black Africans, with little known about its prevalen...

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Plos Genetics : Role of Ctcf Protein in Regulating Fmr1 Locus Tran...

By: Christopher E. Pearson

Description : Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, is caused by epigenetic silencing of the FMR1 gene, through expansion and methylation of a CGG triplet repeat (methylated full mutation). An antisense transcript (FMR1- AS1), starting from both promoter and intron 2 of the FMR1 gene, was demonstrated in transcriptionally active alleles, but not in silent FXS alleles. Moreover, a DNA methylation boundary, which is lost in FXS, ...

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Plos Genetics : C. Elegansnucleostemin is Required for Larval Grow...

By: Stuart K. Kim

Description : The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell–specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogen...

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Plos Genetics : Integrating Genetic and Network Analysis to Charac...

By: Greg Gibson

Description : Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loc...

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Plos Genetics : Increased Life Span Due to Calorie Restriction in ...

By: Stuart Kim

Description : A model for replicative life span extension by calorie restriction (CR) in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NADþ–dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NADþ or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been propose...

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Plos Genetics : Repetitive Element-mediated Recombination as a Mec...

By: R. Scott Hawley

Description : Previous studies of repetitive elements (REs) have implicated a mechanistic role in generating new chimerical genes. Such examples are consistent with the classic model for exon shuffling, which relies on non-homologous recombination. However, recent data for chromosomal aberrations in model organisms suggest that ectopic homology-dependent recombination may also be important. Lack of a dataset comprising experimentally verified young duplicates has hampere...

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Plos Genetics : the Specificity and Flexibility of L1 Reverse Tran...

By: Tom Eickbush

Description : L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP) first uses its endonuclease (EN) to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A) tail, a process known as target-primed reverse transcription (TPRT). Prior studies demonstrated that most L1 insertions occur into sequences related to th...

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