oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2020 ( 72 )

2019 ( 312 )

2018 ( 307 )

2017 ( 338 )

Custom range...

Search Results: 1 - 10 of 176458 matches for " Peter B Becker "
All listed articles are free for downloading (OA Articles)
Page 1 /176458
Display every page Item
Dosage compensation and the global re-balancing of aneuploid genomes
Matthias Prestel, Christian Feller, Peter B Becker
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-8-216
Abstract: Complex genomes are more than just the sum of their genes, but are rather complex regulatory systems in which the expression of each individual gene is a function of the activity of many other genes, so that the levels of their protein products are maintained within a narrow range. Such homeostasis favors the maintenance of the appropriate stoichiometry of subunits in multiprotein complexes or of components in signal transduction pathways, and defines the 'ground state' of a cell [1]. In diploid genomes, both alleles of a gene are usually active and this 'double dose' of each gene is figured into the equation. Thus, deviations from diploidy, such as the deletion or duplication of genes or of larger chromosomal fragments (aneuploidy), unbalance the finely tuned expression of the genome. Segmental aneuploidies of this kind can arise from failed or faulty repair of chromosomal damage due to irradiation, chemical insult or perturbation of replication, or from illegitimate recombination during meiosis. Loss or duplication of entire chromosomes (monosomy or trisomy, respectively) can arise from non-disjunction during cell division. Depending on the extent of the aneuploidy and on the genes affected, the fine balance of trans-acting factors and their chromosomal binding sites that define the gene-expression system is disturbed, and the fitness of the cell or organism challenged.Often, aneuploidies have been associated with a variety of developmental defects and malignant aberrations, such as Down syndrome or certain breast cancers (reviewed in [2,3]). The phenotypes associated with changes in gene copy number can not only be the result of the deregulation of the affected gene(s), but may also reflect trans-acting effects on other chromosomal loci or even more global alterations of the entire regulatory system. This is particularly true if genes coding for regulatory factors, such as transcription factors, are affected (reviewed in [4,5]).Genome-wide studies in different or
Optimal Binary Search Trees with Near Minimal Height
Peter Becker
Computer Science , 2010,
Abstract: Suppose we have n keys, n access probabilities for the keys, and n+1 access probabilities for the gaps between the keys. Let h_min(n) be the minimal height of a binary search tree for n keys. We consider the problem to construct an optimal binary search tree with near minimal height, i.e.\ with height h <= h_min(n) + Delta for some fixed Delta. It is shown, that for any fixed Delta optimal binary search trees with near minimal height can be constructed in time O(n^2). This is as fast as in the unrestricted case. So far, the best known algorithms for the construction of height-restricted optimal binary search trees have running time O(L n^2), whereby L is the maximal permitted height. Compared to these algorithms our algorithm is at least faster by a factor of log n, because L is lower bounded by log n.
Global Analysis of the Relationship between JIL-1 Kinase and Transcription
Catherine Regnard,Tobias Straub,Angelika Mitterweger,Ina K. Dahlsveen,Viola Fabian,Peter B. Becker
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1001327
Abstract: The ubiquitous tandem kinase JIL-1 is essential for Drosophila development. Its role in defining decondensed domains of larval polytene chromosomes is well established, but its involvement in transcription regulation has remained controversial. For a first comprehensive molecular characterisation of JIL-1, we generated a high-resolution, chromosome-wide interaction profile of the kinase in Drosophila cells and determined its role in transcription. JIL-1 binds active genes along their entire length. The presence of the kinase is not proportional to average transcription levels or polymerase density. Comparison of JIL-1 association with elongating RNA polymerase and a variety of histone modifications suggests two distinct targeting principles. A basal level of JIL-1 binding can be defined that correlates best with the methylation of histone H3 at lysine 36, a mark that is placed co-transcriptionally. The additional acetylation of H4K16 defines a second state characterised by approximately twofold elevated JIL-1 levels, which is particularly prominent on the dosage-compensated male X chromosome. Phosphorylation of the histone H3 N-terminus by JIL-1 in vitro is compatible with other tail modifications. In vivo, phosphorylation of H3 at serine 10, together with acetylation at lysine 14, creates a composite histone mark that is enriched at JIL-1 binding regions. Its depletion by RNA interference leads to a modest, but significant, decrease of transcription from the male X chromosome. Collectively, the results suggest that JIL-1 participates in a complex histone modification network that characterises active, decondensed chromatin. We hypothesise that one specific role of JIL-1 may be to reinforce, rather than to establish, the status of active chromatin through the phosphorylation of histone H3 at serine 10.
The Chromosomal High-Affinity Binding Sites for the Drosophila Dosage Compensation Complex
Tobias Straub,Charlotte Grimaud,Gregor D. Gilfillan,Angelika Mitterweger,Peter B. Becker
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000302
Abstract: Dosage compensation in male Drosophila relies on the X chromosome–specific recruitment of a chromatin-modifying machinery, the dosage compensation complex (DCC). The principles that assure selective targeting of the DCC are unknown. According to a prevalent model, X chromosome targeting is initiated by recruitment of the DCC core components, MSL1 and MSL2, to a limited number of so-called “high-affinity sites” (HAS). Only very few such sites are known at the DNA sequence level, which has precluded the definition of DCC targeting principles. Combining RNA interference against DCC subunits, limited crosslinking, and chromatin immunoprecipitation coupled to probing high-resolution DNA microarrays, we identified a set of 131 HAS for MSL1 and MSL2 and confirmed their properties by various means. The HAS sites are distributed all over the X chromosome and are functionally important, since the extent of dosage compensation of a given gene and its proximity to a HAS are positively correlated. The sites are mainly located on non-coding parts of genes and predominantly map to regions that are devoid of nucleosomes. In contrast, the bulk of DCC binding is in coding regions and is marked by histone H3K36 methylation. Within the HAS, repetitive DNA sequences mainly based on GA and CA dinucleotides are enriched. Interestingly, DCC subcomplexes bind a small number of autosomal locations with similar features.
Targeting Determinants of Dosage Compensation in Drosophila
Ina K Dahlsveen,Gregor D Gilfillan,Vladimir I Shelest,Rosemarie Lamm,Peter B Becker
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020005
Abstract: The dosage compensation complex (DCC) in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high- and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs.
Site-specific acetylation of ISWI by GCN5
Roger Ferreira, Anton Eberharter, Tiziana Bonaldi, Mariacristina Chioda, Axel Imhof, Peter B Becker
BMC Molecular Biology , 2007, DOI: 10.1186/1471-2199-8-73
Abstract: We found further diversification of remodelling factors by posttranslational modification. The histone acetyltransferase GCN5 can acetylate the Drosophila remodelling ATPase ISWI at a single, conserved lysine, K753, in vivo and in vitro. The target sequence is strikingly similar to the N-terminus of histone H3, where the corresponding lysine, H3K14, can also be acetylated by GCN5. The acetylated form of ISWI represents a minor species presumably associated with the nucleosome remodelling factor NURF.Acetylation of histone H3 and ISWI by GCN5 is explained by the sequence similarity between the histone and ISWI around the acetylation site. The common motif RKT/SxGx(Kac)xPR/K differs from the previously suggested GCN5/PCAF recognition motif GKxxP. This raises the possibility of co-regulation of a nucleosome remodelling factor and its nucleosome substrate through acetylation of related epitopes and suggests a direct crosstalk between two distinct nucleosome modification principles.Disruption of DNA-histone interactions by nucleosome remodelling ATPases may lead to a variety of transitions of chromatin structure, such as the partial or complete disassembly of nucleosomes, the exchange of histones, or the sliding of intact histone octamers on DNA [1-4]. In many cases their activity is focused on local disruption of the nucleosomal fibre through recruitment of DNA-binding regulators to promote access of factors further downstream in the cascade of events that leads to promoter opening [2]. However, genome-wide processes like replication, DNA damage responses or homologous recombination require chromatin to be dynamic on a global scale. In addition to generating local access to nucleosomal DNA, nucleosome disruption may also have profound consequences for the folding of the nucleosomal fibre into higher order structures [5,6].One largely unresolved issue to date is how the activity of chromatin remodelling enzymes is regulated. Established regulatory principles that govern,
The Galactic Wind Haze and its $\gamma$-spectrum
Gupta, Nayantara;Nath, Biman B.;Biermann, Peter L.;Seo, Eun -Suk;Stanev, Todor;Tjus, Julia Becker
High Energy Physics - Phenomenology , 2013,
Abstract: The spectrum observed by Fermi-LAT from the Galactic centre region shows a gamma ray feature near 130 GeV, that in some analyses appears as a possible line. We discuss the possibility that this gamma ray feature has a cosmic ray origin. We argue that the cosmic ray electrons steepen near 1 TeV from $E^{-3}$ to about $E^{-4.2}$, and are all secondary derived from the knee-feature of normal cosmic rays. We argue that the observed feature at $\sim 130$ GeV could essentially be a noise feature on top of a sharp turn-off in the $\gamma$ ray spectrum at $\sim 130$ GeV. This match suggests that the knee of normal cosmic rays is the same everywhere in the Galaxy. We suggest that it follows that all supernovae contributing give the same cosmic ray spectrum, with the knee feature given by common stellar properties; in fact, this is consistent with the supernova theory proposed by Bisnovatyi-Kogan (1970), a magneto-rotational mechanism: Massive stars converge to common properties in terms of rotation and magnetic fields just before they explode.
The Galactic Wind Haze and its $γ$-spectrum
Nayantara Gupta,Biman B. Nath,Peter L. Biermann,Eun -Suk Seo,Todor Stanev,Julia Becker Tjus
Physics , 2013,
Abstract: We study the possibility that the gamma ray emission in the Fermi bubbles observed is produced by cosmic ray electrons with a spectrum similar to Galactic cosmic rays. We argue that the cosmic ray electrons steepen near 1 TeV from $E^{-3}$ to about $E^{-4.2}$, and are partially secondaries derived from the knee-feature of normal cosmic rays. We speculate that the observed feature at $\sim 130$ GeV could essentially be due to inverse Compton emission off a pair-production peak on top of a turn-off in the $\gamma$ ray spectrum at $\sim 130$ GeV. It suggests that the knee of normal cosmic rays is the same everywhere in the Galaxy. A consequence could be that all supernovae contributing give the same cosmic ray spectrum, with the knee feature given by common stellar properties; in fact, this is consistent with the supernova theory proposed by Bisnovatyi-Kogan (1970), a magneto-rotational mechanism, if massive stars converge to common properties in terms of rotation and magnetic fields just before they explode.
Phosphorylation of SU(VAR)3–9 by the Chromosomal Kinase JIL-1
Joern Boeke,Catherine Regnard,Weili Cai,J?rgen Johansen,Kristen M. Johansen,Peter B. Becker,Axel Imhof
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010042
Abstract: The histone methyltransferase SU(VAR)3–9 plays an important role in the formation of heterochromatin within the eukaryotic nucleus. Several studies have shown that the formation of condensed chromatin is highly regulated during development, suggesting that SU(VAR)3–9's activity is regulated as well. However, no mechanism by which this may be achieved has been reported so far. As we and others had shown previously that the N-terminus of SU(VAR)3–9 plays an important role for its activity, we purified interaction partners from Drosophila embryo nuclear extract using as bait a GST fusion protein containing the SU(VAR)3–9 N-terminus. Among several other proteins known to bind Su(VAR)3–9 we isolated the chromosomal kinase JIL-1 as a strong interactor. We show that SU(VAR)3–9 is a substrate for JIL-1 in vitro as well as in vivo and map the site of phosphorylation. These findings may provide a molecular explanation for the observed genetic interaction between SU(VAR)3–9 and JIL-1.
Cloning of the Repertoire of Individual Plasmodium falciparum var Genes Using Transformation Associated Recombination (TAR)
Annette Gaida,Marion M. Becker,Christoph D. Schmid,Tobias Bühlmann,Edward J. Louis,Hans-Peter Beck
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017782
Abstract: One of the major virulence factors of the malaria causing parasite is the Plasmodium falciparum encoded erythrocyte membrane protein 1 (PfEMP1). It is translocated to It the membrane of infected erythrocytes and expressed from approximately 60 var genes in a mutually exclusive manner. Switching of var genes allows the parasite to alter functional and antigenic properties of infected erythrocytes, to escape the immune defense and to establish chronic infections. We have developed an efficient method for isolating VAR genes from telomeric and other genome locations by adapting transformation-associated recombination (TAR) cloning, which can then be analyzed and sequenced. For this purpose, three plasmids each containing a homologous sequence representing the upstream regions of the group A, B, and C var genes and a sequence homologous to the conserved acidic terminal segment (ATS) of var genes were generated. Co-transfection with P. falciparum strain ITG2F6 genomic DNA in yeast cells yielded 200 TAR clones. The relative frequencies of clones from each group were not biased. Clones were screened by PCR, as well as Southern blotting, which revealed clones missed by PCR due to sequence mismatches with the primers. Selected clones were transformed into E. coli and further analyzed by RFLP and end sequencing. Physical analysis of 36 clones revealed 27 distinct types potentially representing 50% of the var gene repertoire. Three clones were selected for sequencing and assembled into single var gene containing contigs. This study demonstrates that it is possible to rapidly obtain the repertoire of var genes from P. falciparum within a single set of cloning experiments. This technique can be applied to individual isolates which will provide a detailed picture of the diversity of var genes in the field. This is a powerful tool to overcome the obstacles with cloning and assembly of multi-gene families by simultaneously cloning each member.
Page 1 /176458
Display every page Item


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