Computational study of associations between histone modification and protein-DNA binding in yeast genome by integrating diverse information

<p>Abstract</p> <p>Background</p> <p>In parallel with the quick development of high-throughput technologies, <it>in vivo (vitro) </it>experiments for genome-wide identification of protein-DNA interactions have been developed. Nevertheless, a few questions remain in the field, such as how to distinguish true protein-DNA binding (functional binding) from non-specific protein-DNA binding (non-functional binding). Previous researches tackled the problem by integrated analysis of multiple available sources. However, few systematic studies have been carried out to examine the possible relationships between histone modification and protein-DNA binding. Here this issue was investigated by using publicly available histone modification data in yeast.</p> <p>Results</p> <p>Two separate histone modification datasets were studied, at both the open reading frame (ORF) and the promoter region of binding targets for 37 yeast transcription factors. Both results revealed a distinct histone modification pattern between the functional protein-DNA binding sites and non-functional ones for almost half of all TFs tested. Such difference is much stronger at the ORF than at the promoter region. In addition, a protein-histone modification interaction pathway can only be inferred from the functional protein binding targets.</p> <p>Conclusions</p> <p>Overall, the results suggest that histone modification information can be used to distinguish the functional protein-DNA binding from the non-functional, and that the regulation of various proteins is controlled by the modification of different histone lysines such as the protein-specific histone modification levels.</p

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors

The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible twoinput- one-output logic gates (e.g. AND or XOR) to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet’s observed gene expression pattern across many conditions. We make Loregic available as a generalpurpose tool (github.com/gersteinlab/loregic). We validate it with known yeast transcriptionfactor knockout experiments. Next, using human ENCODE ChIP-Seq and TCGA RNA-Seq data, we are able to demonstrate how Loregic characterizes complex circuits involving both proximally and distally regulating transcription factors (TFs) and also miRNAs. Furthermore, we show that MYC, a well-known oncogenic driving TF, can be modeled as acting independently from other TFs (e.g., using OR gates) but antagonistically with repressing miRNAs. Finally, we inter-relate Loregic’s gate logic with other aspects of regulation, such as indirect binding via protein-protein interactions, feed-forward loop motifs and global regulatory hierarchy

Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants

Summary Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4+ T-cell subsets, regulatory T-cells, CD8+ T-cells, B-cells, and monocytes. We find that ~90% of causal variants are noncoding, with ~60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10–20% directly alter recognizable transcription factor binding motifs. Rather, most noncoding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models

Bond strength of adhesive systems to human tooth enamel Resistência adesiva de sistemas adesivos ao esmalte dentário humano

The purpose of this study was to evaluate in vitro three adhesive systems: a total etching single-component system (G1 Prime & Bond 2.1), a self-etching primer (G2 Clearfil SE Bond), and a self-etching adhesive (G3 One Up Bond F), through shear bond strength to enamel of human teeth, evaluating the type of fracture through stereomicroscopy, following the ISO guidance on adhesive testing. Thirty sound premolars were bisected mesiodistally and the buccal and lingual surfaces were embedded in acrylic resin, polished up to 600-grit sandpapers, and randomly assigned to three experimental groups (n = 20). Composite resin cylinders were added to the tested surfaces. The specimens were kept in distilled water (37&deg;C/24 h), thermocycled for 500 cycles (5&deg;C-55&deg;C) and submitted to shear testing at a crosshead speed of 0.5 mm/min. The type of fracture was analyzed under stereomicroscopy and the data were submitted to Anova, Tukey and Chi-squared (5%) statistical analyses. The mean adhesive strengths were G1: 18.13 &plusmn; 6.49 MPa, (55% of resin cohesive fractures); G2: 17.12 &plusmn; 5.80 MPa (90% of adhesive fractures); and G3: 10.47 &plusmn; 3.14 MPa (85% of adhesive fractures). In terms of bond strength, there were no significant differences between G1 and G2, and G3 was significantly different from the other groups. G1 presented a different type of fracture from that of G2 and G3. In conclusion, although the total etching and self-etching systems presented similar shear bond strength values, the types of fracture presented by them were different, which can have clinical implications.<br>O objetivo deste estudo foi avaliar in vitro três sistemas adesivos: um monocomponente com condicionamento ácido total (G1 Prime & Bond 2.1), um "primer" autocondicionante (G2 Clearfil SE Bond) e um adesivo autocondicionante (G3 One Up Bond F), através de resistência ao cisalhamento ao esmalte de dentes humanos, avaliando o tipo de fratura por estereomicroscopia, seguindo as normas ISO para testes adesivos. Trinta pré-molares hígidos foram seccionados ao meio em sentido mésio-distal, incluídos em resina acrílica, polidos até lixa d'água de granulação 600 e aleatoriamente divididos em três grupos (n = 20). Cilindros de resina composta foram adicionados às superfícies de teste. Os espécimes foram armazenados em água destilada (37&deg;C/24 h), termociclados por 500 ciclos (5&deg;C-55&deg;C) e submetidos ao teste de cisalhamento com velocidade de 0,5 mm/min, sendo o tipo de fratura analisado sob estereomicroscopia e os dados submetidos à análise estatística Anova, Tukey e Qui-quadrado (5%). As médias de resistência adesiva foram: G1: 18,13 &plusmn; 6,49 MPa, (55% de fraturas coesivas em resina); G2: 17,12 &plusmn; 5,80 MPa (90% de fraturas adesivas) e G3 10,47 &plusmn; 3,14 MPa (85% de fraturas adesivas). Em termos de resistência adesiva, não houve diferenças significantes entre G1 e G2, tendo G3 apresentado diferença significante em relação aos demais grupos. G1 apresentou tipo de fratura diferente de G2 e G3. Em conclusão, apesar de os sistemas adesivos com condicionamento ácido total e "primer" autocondicionante terem apresentado valores de resistência adesiva similares, o tipo de fratura apresentado por eles foi diferente, o que pode ter implicações clínicas