Transcription Initiation Activity Sets Replication Origin Efficiency in Mammalian Cells

Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cells

Predictability and trapping under conditions of globalization and agricultural trade : an application of the CDS approach

The purpose of the paper is to demonstrate how timely investments in the ecosphere promote high level stable agricultural income. It is shown that the recovery capability of the ecosphere together with strong agricultural productivity relative to the rest of the economy may be considered as control parameters of the system. They play a crucial role for agriculture to escape from a low level trap. The scenario leading to the escape is based on an economic strategy leading to a sequence of local and global bifurcations, changing the dynamical structure of the system. The effects of globalization on the system’s dynamics and stable sets are considered. Globalization is taken into account by means of nonautonomous impulses making selected system parameters oscillate. Necessary conditions for sustainable agriculture development are established