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Gene activity is not only determined by processes occurring very close to or at the gene, such as transcription factor or RNA Polymerase II (PolII) binding. A multitude of past observations such as the localization of inactive chromatin to the nuclear periphery and active chromatin in the centre of the nucleus, the clustering of highly transcribed genes at transcriptional hotspots as well as the looping of active genes out of the chromosome territory made clear that the ‘context matters’ and the 3-dimensional organization of the chromatin fibre is fundamental for genome function. Here we want to review whether and how the different architectural levels that were recently identified by high-throughput chromatin conformation capturing techniques influence transcription. [ABSTRACT FROM AUTHOR]

Regulatory DNA elements such as enhancers, silencers and insulators are embedded in metazoan genomes, and they control gene expression during development. Although they fulfil different roles, they share specific properties. Herein we discuss some examples and a parsimonious model for their function is proposed. All are transcription units that tether their target promoters close to, or distant from, transcriptional hot spots (or 'factories'). [ABSTRACT FROM AUTHOR]

The sequential organization of genomes, i.e. the relations between distant base pairs and regions within sequences, and its connection to the three-dimensional organization of genomes is still a largely unresolved problem. Long-range power-law correlations were found using correlation analysis on almost the entire observable scale of 132 completely sequenced chromosomes of 0.5 × 106 to 3.0 × 107 bp from Archaea, Bacteria, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, and Homo sapiens. The local correlation coefficients show a species-specific multi-scaling behaviour: close to random correlations on the scale of a few base pairs, a first maximum from 40 to 3,400 bp (for Arabidopsis thaliana and Drosophila melanogaster divided in two submaxima), and often a region of one or more second maxima from 105 to 3 × 105 bp. Within this multi-scaling behaviour, an additional fine-structure is present and attributable to codon usage in all except the human sequences, where it is related to nucleosomal binding. Computer-generated random sequences assuming a block organization of genomes, the codon usage, and nucleosomal binding explain these results. Mutation by sequence reshuffling destroyed all correlations. Thus, the stability of correlations seems to be evolutionarily tightly controlled and connected to the spatial genome organization, especially on large scales. In summary, genomes show a complex sequential organization related closely to their three-dimensional organization. [ABSTRACT FROM AUTHOR]

Summary: The current fast growth of genome-wide association studies (GWAS) combined with now common computationally expensive imputation requires the online access of large user groups to high-performance computing resources capable of analyzing rapidly and efficiently millions of genetic markers for ten thousands of individuals. Here, we present a web-based interface—called GRIMP—to run publicly available genetic software for extremely large GWAS on scalable super-computing grid infrastructures. This is of major importance for the enlargement of GWAS with the availability of whole-genome sequence data from the 1000 Genomes Project and for future whole-population efforts. [ABSTRACT FROM PUBLISHER]