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Already for thousands of years mankind is aware of inheritance and its manipulation by mating and breeding. The discovery of the cell nucleus by A. van Leeuwenhook in the 17th century marks a start to elucidate the epically discussed evolutionary transfer of information in detail. Now after more than 170 years of research on the 3D architecture and dynamics of genomes and the co-evolved interaction networks of regulatory elements creating genome function - i.e. the storage, replication, and expression of genetic information—a consistent systems statistical mechanics genomics framework emerges for the first time. Obviously the structure and function of genomes co-evolved as an inseparable system allowing the physical storage, expression, and replication of genetic information. The DNA double helix and the nucleosome had been determined structurally at the very highest level already, including genome sequences and epigenetic histone modifications. That chromosomes form territories with functional relevant positioning within the cell nucleus and that chromosomal subdomains exist has been also determined to a fair degree of detail. Only recently, however, we were finally able to fill the much debated gap in-between by establishing that nucleosomes compact into a quasi-fibre folded into stable loops which form stable multi-loop aggregates/rosettes connected by linkers and hence creating chromosome arms and entire chromosomes. Interestingly, this has lead immediately to a consistent and cross-proven systems statistical mechanics genomic framework which is balancing stability/flexibility ensuring genome integrity, enabling expression/regulation of genetic information, as well as genome replication - all this in evolutionary perspectives as the natural outcome of Darwinian natural selection and Lamarkian self-referenced manipulation. Thus, genotype and phenotype are multilisticly entangled and beyond are embedded in genome ecology i(!)n- and environments. This not only opens the door to a true universal sequencing of genetic information, but also is the key for a general understanding of genomes, their function and evolution, as well as for applied diagnostics and treatment of disease, for future genome manipulation and engineering efforts, as far as the creation of artificial or extra-terrestrial live contexts.

Additional file 18: Table S6. General consensus loop sizes and thus position relative to the start of the first loop at the first loop base determined for mouse MEL cells of one part of the Igh locus at MM 12q F1-F2. The subchromosomal domain size is calculated for domains with defined borders only from the sum of the loop sizes present.

Additional file 1. Â Additional documentation.

Background: The rearrangement of nucleosomes along the DNA fiber profoundly affects gene expression, but little is known about how signalling reshapes the chromatin landscape, in three-dimensional space and over time, to allow establishment of new transcriptional programs. Results: Using micrococcal nuclease treatment and high-throughput sequencing, we map genome-wide changes in nucleosome positioning in primary human endothelial cells stimulated with tumour necrosis factor alpha (TNF alpha) - a proinflammatory cytokine that signals through nuclear factor kappa-B (NF-kappa B). Within 10 min, nucleosomes reposition at regions both proximal and distal to NF-kappa B binding sites, before the transcription factor quantitatively binds thereon. Similarly, in long TNF alpha-responsive genes, repositioning precedes transcription by pioneering elongating polymerases and appears to nucleate from intragenic enhancer clusters resembling super-enhancers. By 30 min, widespread repositioning throughout megabase pair-long chromosomal segments, with consequential effects on three-dimensional structure (detected using chromosome conformation capture), is seen. Conclusions: Whilst nucleosome repositioning is viewed as a local phenomenon, our results point to effects occurring over multiple scales. Here, we present data in support of a TNF alpha-induced priming mechanism, mostly independent of NF-kappa B binding and/or elongating RNA polymerases, leading to a plastic network of interactions that affects DNA accessibility over large domains.

The chromatin architecture is constantly changing because of cellular processes such as proliferation, differentiation and changes in the expression profile during gene activation or silencing. Unravelling the changes that occur in the chromatin structure during these processes has been a topic of interest for many years. It is known that gene activation of large gene loci is thought to occur by means of an active looping mechanism. It was also shown for the beta-globin locus that the gene promoter interacts with an active chromatin hub by means of an active looping mechanism. This means that the locus changes in three-dimensional (3D) nuclear volume and chromatin shape. As a means of visualizing and measuring these dynamic changes in chromatin structure of the beta-globin locus, we used a 3D DNA-FISH method in combination with 3D image acquisition to volume render fluorescent signals into 3D objects. These 3D chromatin structures were geometrically analysed, and results prior to and after gene activation were quantitatively compared. Confocal and super-resolution imaging revealed that the inactive locus occurs in several different conformations. These conformations change in shape and surface structure upon cell differentiation into a more folded and rounded structure that has a substantially smaller size and volume. These physical measurements represent the first non-biochemical evidence that, upon gene activation, an actively transcribing chromatin hub is formed by means of additional chromatin looping.

Sustained Renewability: Approached by Systems Theory and Human Ecology