oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 1 )

2017 ( 2 )

2016 ( 2 )

2015 ( 38 )

Custom range...

Search Results: 1 - 10 of 465 matches for " Corey Nislow "
All listed articles are free for downloading (OA Articles)
Page 1 /465
Display every page Item
Diversity of Eukaryotic DNA Replication Origins Revealed by Genome-Wide Analysis of Chromatin Structure
Nicolas M. Berbenetz,Corey Nislow ,Grant W. Brown
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001092
Abstract: Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers) positions nucleosomes adjacent to the origin to promote replication origin function.
Response to “The Reality of Pervasive Transcription”
Harm van Bakel,Corey Nislow,Benjamin J. Blencowe,Timothy R. Hughes
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001102
Abstract:
Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast
Elke Ericson,Marinella Gebbia,Lawrence E. Heisler,Jan Wildenhain,Mike Tyers,Guri Giaever,Corey Nislow
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000151
Abstract: To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.
Most “Dark Matter” Transcripts Are Associated With Known Genes
Harm van Bakel,Corey Nislow,Benjamin J. Blencowe,Timothy R. Hughes
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000371
Abstract: A series of reports over the last few years have indicated that a much larger portion of the mammalian genome is transcribed than can be accounted for by currently annotated genes, but the quantity and nature of these additional transcripts remains unclear. Here, we have used data from single- and paired-end RNA-Seq and tiling arrays to assess the quantity and composition of transcripts in PolyA+ RNA from human and mouse tissues. Relative to tiling arrays, RNA-Seq identifies many fewer transcribed regions (“seqfrags”) outside known exons and ncRNAs. Most nonexonic seqfrags are in introns, raising the possibility that they are fragments of pre-mRNAs. The chromosomal locations of the majority of intergenic seqfrags in RNA-Seq data are near known genes, consistent with alternative cleavage and polyadenylation site usage, promoter- and terminator-associated transcripts, or new alternative exons; indeed, reads that bridge splice sites identified 4,544 new exons, affecting 3,554 genes. Most of the remaining seqfrags correspond to either single reads that display characteristics of random sampling from a low-level background or several thousand small transcripts (median length = 111 bp) present at higher levels, which also tend to display sequence conservation and originate from regions with open chromatin. We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known exons, and the genome is not as pervasively transcribed as previously reported.
Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action
Maureen E Hillenmeyer, Elke Ericson, Ronald W Davis, Corey Nislow, Daphne Koller, Guri Giaever
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-3-r30
Abstract: Yeast competitive fitness data constitute a unique, genome-wide assay of the cellular response to environmental and chemical perturbations [1-8]. Here, we systematically analyzed the largest fitness dataset available, comprising measurements of the growth rates of barcoded, pooled deletion strains in the presence of over 400 unique perturbations [1] and show that the dataset reveals novel aspects of cellular physiology and provides a valuable resource for systems biology. In the haploinsufficiency profiling (HIP) assay consisting of all 6,000 heterozygous deletions (where one copy of each gene is deleted), most strains (97%) grow at the rate of wild type [9] when assayed in parallel. In the presence of a drug, the strain deleted for the drug target is specifically sensitized (as measured by a decrease in growth rate) as a result of a further decrease in 'functional' gene dosage by the drug binding to the target protein. In this way, fitness data allow identification of the potential drug target [3,4,10]. In the homozygous profiling (HOP) assay (applied to non-essential genes), both copies of the gene are deleted in a diploid strain to produce a complete loss-of-function allele. This assay identifies genes required for growth in the presence of compound, often identifying functions that buffer the drug target pathway [5-8].The field of functional genomics aims to predict gene functions using high-throughput datasets that interrogate functional genetic relationships. To address the value of fitness data as a resource for functional genomics, we asked how well co-fitness (correlated growth of gene deletion strains in compounds) predicts gene function compared to other large-scale datasets, including co-expression, protein-protein interactions, and synthetic lethality [11-13]. Interestingly, co-fitness predicts cellular functions not evident in these other datasets. We also investigated the theory that genes are essential because they belong to essential complexes [14,1
A comparative analysis of DNA barcode microarray feature size
Ron Ammar, Andrew M Smith, Lawrence E Heisler, Guri Giaever, Corey Nislow
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-471
Abstract: We demonstrate that barcode microarrays with smaller features are equally capable of detecting variation in DNA barcode intensity when compared to larger feature sizes within a specific microarray platform. The barcodes used in this study are the well-characterized set derived from the Yeast KnockOut (YKO) collection used for screens of pooled yeast (Saccharomyces cerevisiae) deletion mutants. We treated these pools with the glycosylation inhibitor tunicamycin as a test compound. Three generations of barcode microarrays at 30, 8 and 5 μm features sizes independently identified the primary target of tunicamycin to be ALG7.We show that the data obtained with 5 μm feature size is of comparable quality to the 30 μm size and propose that further shrinking of features could yield barcode microarrays with equal or greater resolving power and, more importantly, higher density.Genome-wide studies often measure changes in the abundance of all gene products over a period of time or under varying conditions. Microarrays have made these studies possible by enabling researchers to monitor all known genes of an organism simultaneously to detect patterns of gene activity [1], alternative splicing variants [2] the presence of single nucleotide polymorphisms [3], the presence of copy number variants and [4] DNA binding sites of diverse proteins [5], among others. One application of microarrays that our laboratory has focused on is the parallel identification of individual molecular barcoded gene deletion mutants grown competitively in pools [6,7]. Through the efforts of the Yeast Deletion Consortium, a Yeast KnockOut (YKO) collection was constructed consisting of approximately 6,000 heterozygous gene deletions (>96% of all annotated open reading frames), of which over 1,100 are known to be essential for growth [7]. The remaining ~5,000 genes are nonessential, created as homozygous deletions and MATαand MATα deletion collections. These collections were made by systematic replacement o
Nucleosome-coupled expression differences in closely-related species
Yuanfang Guan, Victoria Yao, Kyle Tsui, Marinella Gebbia, Maitreya J Dunham, Corey Nislow, Olga G Troyanskaya
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-466
Abstract: We address this challenge by generating nucleosome positioning and cell cycle expression data for Saccharomyces bayanus and show that differences in nucleosome occupancy reflect cell cycle expression divergence between two yeast species, S. bayanus and S. cerevisiae. Specifically, genes with nucleosome-depleted MBP1 motifs upstream of their coding sequence show periodic expression during the cell cycle, whereas genes with nucleosome-shielded motifs do not. In addition, conserved cell cycle regulatory motifs across these two species are more nucleosome-depleted compared to those that are not conserved, suggesting that the degree of conservation of regulatory sites varies, and is reflected by nucleosome occupancy patterns. Finally, many changes in cell cycle gene expression patterns across species can be correlated to changes in nucleosome occupancy on motifs (rather than to the presence or absence of motifs).Our observations suggest that alteration of nucleosome occupancy is a previously uncharacterized feature related to the divergence of cell cycle expression between species.An organism's DNA contains numerous regulatory sequences that are used to modulate gene expression; yet DNA sequence alone does not explain why some regulatory sequences are functional while others are not. Because most genomic DNA (80% on average) is tightly packaged into nucleosomes [1], alternating nucleosome occupancy has been proposed as an important strategy to regulate gene expression since its initial discovery [2,3]. Indeed, higher expression levels are commonly associated with nucleosome depletion at promoters and other genomic locations, e.g. rDNA [1,4-6]. It has also been demonstrated that nucleosome occupancy affects the accessibility of DNA sequence motifs to transcriptional regulators; as a consequence different DNA sequences can display different nucleosome occupancy levels [1,4,7]. Further, motifs recognized and bound by active transcription factors are more likely to be nucleo
Response to “The Reality of Pervasive Transcription”
Harm van Bakel,Corey Nislow,Benjamin J. Blencowe,Timothy R. Hughes
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1001102
Abstract:
Most “Dark Matter” Transcripts Are Associated With Known Genes
Harm van Bakel,Corey Nislow,Benjamin J. Blencowe,Timothy R. Hughes
PLOS Biology , 2010, DOI: 10.1371/journal.pbio.1000371
Abstract: A series of reports over the last few years have indicated that a much larger portion of the mammalian genome is transcribed than can be accounted for by currently annotated genes, but the quantity and nature of these additional transcripts remains unclear. Here, we have used data from single- and paired-end RNA-Seq and tiling arrays to assess the quantity and composition of transcripts in PolyA+ RNA from human and mouse tissues. Relative to tiling arrays, RNA-Seq identifies many fewer transcribed regions (“seqfrags”) outside known exons and ncRNAs. Most nonexonic seqfrags are in introns, raising the possibility that they are fragments of pre-mRNAs. The chromosomal locations of the majority of intergenic seqfrags in RNA-Seq data are near known genes, consistent with alternative cleavage and polyadenylation site usage, promoter- and terminator-associated transcripts, or new alternative exons; indeed, reads that bridge splice sites identified 4,544 new exons, affecting 3,554 genes. Most of the remaining seqfrags correspond to either single reads that display characteristics of random sampling from a low-level background or several thousand small transcripts (median length = 111 bp) present at higher levels, which also tend to display sequence conservation and originate from regions with open chromatin. We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known exons, and the genome is not as pervasively transcribed as previously reported.
Conserved Substitution Patterns around Nucleosome Footprints in Eukaryotes and Archaea Derive from Frequent Nucleosome Repositioning through Evolution
Tobias Warnecke ,Erin A. Becker,Marc T. Facciotti,Corey Nislow,Ben Lehner
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1003373
Abstract: Nucleosomes, the basic repeat units of eukaryotic chromatin, have been suggested to influence the evolution of eukaryotic genomes, both by altering the propensity of DNA to mutate and by selection acting to maintain or exclude nucleosomes in particular locations. Contrary to the popular idea that nucleosomes are unique to eukaryotes, histone proteins have also been discovered in some archaeal genomes. Archaeal nucleosomes, however, are quite unlike their eukaryotic counterparts in many respects, including their assembly into tetramers (rather than octamers) from histone proteins that lack N- and C-terminal tails. Here, we show that despite these fundamental differences the association between nucleosome footprints and sequence evolution is strikingly conserved between humans and the model archaeon Haloferax volcanii. In light of this finding we examine whether selection or mutation can explain concordant substitution patterns in the two kingdoms. Unexpectedly, we find that neither the mutation nor the selection model are sufficient to explain the observed association between nucleosomes and sequence divergence. Instead, we demonstrate that nucleosome-associated substitution patterns are more consistent with a third model where sequence divergence results in frequent repositioning of nucleosomes during evolution. Indeed, we show that nucleosome repositioning is both necessary and largely sufficient to explain the association between current nucleosome positions and biased substitution patterns. This finding highlights the importance of considering the direction of causality between genetic and epigenetic change.
Page 1 /465
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.