NXSensor web tool for evaluating DNA for nucleosome exclusion sequences and accessibility to binding factors

Nucleosomes, a basic structural unit of eukaryotic chromatin, play a significant role in regulating gene expression. We have developed a web tool based on DNA sequences known from empirical and theoretical studies to influence DNA bending and flexibility, and to exclude nucleosomes. NXSensor (available at ) finds nucleosome exclusion sequences, evaluates their length and spacing, and computes an ‘accessibility score’ giving the proportion of base pairs likely to be nucleosome-free. Application of NXSensor to the promoter regions of housekeeping (HK) genes and those of tissue-specific (TS) genes revealed a significant difference between the two classes of gene, the former being significantly more open, on average, particularly near transcription start sites (TSSs). NXSensor should be a useful tool in assessing the likelihood of nucleosome formation in regions involved in gene regulation and other aspects of chromatin function

Prediction and analysis of nucleosome exclusion regions in the human genome

<p>Abstract</p> <p>Background</p> <p>Nucleosomes are the basic structural units of eukaryotic chromatin, and they play a significant role in regulating gene expression. Specific DNA sequence patterns are known, from empirical and theoretical studies, to influence DNA bending and flexibility, and have been shown to exclude nucleosomes. A whole genome localization of these patterns, and their analysis, can add important insights on the gene regulation mechanisms that depend upon the structure of chromatin in and around a gene.</p> <p>Results</p> <p>A whole genome annotation for nucleosome exclusion regions (NXRegions) was carried out on the human genome. Nucleosome exclusion scores (NXScores) were calculated individually for each nucleotide, giving a measure of how likely a specific nucleotide and its immediate neighborhood would impair DNA bending and, consequently, exclude nucleosomes. The resulting annotations were correlated with 19055 gene expression profiles. We developed a new method based on Grubbs' outliers test for ranking genes based on their tissue specificity, and correlated this ranking with NXScores. The results show a strong correlation between tissue specificity of a gene and the propensity of its promoter to exclude nucleosomes (the promoter region was taken as -1500 to +500 bp from the RefSeq-annotated transcription start site). In addition, NXScores correlated well with gene density, gene expression levels, and DNaseI hypersensitive sites.</p> <p>Conclusion</p> <p>We present, for the first time, a whole genome prediction of nucleosome exclusion regions for the human genome (the data are available for download from Additional Materials). Nucleosome exclusion patterns are correlated with various factors that regulate gene expression, which emphasizes the need to include chromatin structural parameters in experimental analysis of gene expression.</p

La diversitat de l'activitat econòmica a la Catalunya Moderna: més enllà de la renda feudal

Escollir com a concepte organitzador d'una ponència la idea de la diversitat i plantejar-lo com a innovador fa pensar que anteriorment els historiadors pensaven en clau d'una Catalunya homogènia, sense diversitat. Segurament tampoc no era ben bé així, però alguns tòpics portaven a pensar-ho: a) L'agricultura, basada en el conreu del cereal, la vinya i l'olivera, era fonamentalment de subsistència, amb baixos rendiments i molt poca comercialització de productes (els masos produïen per consumir, no per vendre).1 No hi havia, per tant, mercat, ni altres models. b) El feudalisme -i el complex entramat de jurisdiccions i drets senyorials- era la pesada llosa que requeia sobre l'agricultura i l'endarreria, desviant part de la producció pagesa i dificultant la transició al capitalisme. És cert que, sobre aquest tema, hi ha hagut un ampli debat sobre el pes del feudalisme a Catalunya: per a uns, la Sentència Arbitral..

GenSensor Suite: A Web-Based Tool for the Analysis of Gene and Protein Interactions, Pathways, and Regulation

The GenSensor Suite consists of four web tools for elucidating relationships among genes and proteins. GenPath results show which biochemical, regulatory, or other gene set categories are over- or under-represented in an input list compared to a background list. All common gene sets are available for searching in GenPath, plus some specialized sets. Users can add custom background lists. GenInteract builds an interaction gene list from a single gene input and then analyzes this in GenPath. GenPubMed uses a PubMed query to identify a list of PubMed IDs, from which a gene list is extracted and queried in GenPath. GenViewer allows the user to query one gene set against another in GenPath. GenPath results are presented with relevant P- and q-values in an uncluttered, fully linked, and integrated table. Users can easily copy this table and paste it directly into a spreadsheet or document

Comparative analysis of genome sequences from four strains of the Buchnera aphidicola Mp endosymbion of the green peach aphid, Myzus persicae

BACKGROUND: Myzus persicae, the green peach aphid, is a polyphagous herbivore that feeds from hundreds of species of mostly dicot crop plants. Like other phloem-feeding aphids, M. persicae rely on the endosymbiotic bacterium, Buchnera aphidicola (Buchnera Mp), for biosynthesis of essential amino acids and other nutrients that are not sufficiently abundant in their phloem sap diet. Tobacco-specialized M. persicae are typically red and somewhat distinct from other lineages of this species. To determine whether the endosymbiotic bacteria of M. persicae could play a role in tobacco adaptation, we sequenced the Buchnera Mp genomes from two tobacco-adapted and two non-tobacco M. persicae lineages. RESULTS: With a genome size of 643.5 kb and 579 predicted genes, Buchnera Mp is the largest Buchnera genome sequenced to date. No differences in gene content were found between the four sequenced Buchnera Mp strains. Compared to Buchnera APS from the well-studied pea aphid, Acyrthosiphon pisum, Buchnera Mp has 21 additional genes. These include genes encoding five enzymes required for biosynthesis of the modified nucleoside queosine, the heme pathway enzyme uroporphyrinogen III synthase, and asparaginase. Asparaginase, which is also encoded by the genome of the aphid host, may allow Buchnera Mp to synthesize essential amino acids from asparagine, a relatively abundant phloem amino acid. CONCLUSIONS: Together our results indicate that the obligate intracellular symbiont Buchnera aphidicola does not contribute to the adaptation of Myzus persicae to feeding on tobacco

Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach

Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD

STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia.Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer.These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such that amino acids liberated by increased proteolysis in cachexia are synthesized into acute phase proteins and exported into the blood