DNA replication origins: from sequence specificity to epigenetics

Site-specific initiation of DNA replication is a conserved function in all organisms. In Escherichia coli and Saccharomyces cerevisiae, DNA replication origins are sequence specific, but in multicellular organisms, origins are not so clearly defined. In this article, I present a model of origin specification by epigenetic mechanisms that allows the establishment of stable chromatin domains, which are characterized by autonomous replication. According to this model, origins of DNA replication help to establish domains of gene expression for the generation of cell diversity.     

Neuroblastoma epigenetics: From candidate gene approaches to genome-wide screenings

Neuroblastoma (NB) is a childhood tumor originating from sympathetic nervous system cells. Although recently new insights into genes involved in NB have emerged, the molecular basis of neuroblastoma development and progression still remains poorly understood. The best-characterized genetic alterations include amplification of the proto-oncogene MYCN, ALK activating mutations or amplification, gain of chromosome arm 17q and losses of 1p, 3p, and 11q. Epigenetic alterations have been described as well: caspase-8 (CASP8) and RAS-association domain family 1 isoform A (RASSF1A) DNA-methylation are important events for the development and progression of neuroblastoma. In total, there are about 75 genes described as epigenetically affected in NB cell lines and/or NB primary samples. These epigenetic alterations were either found using a candidate gene approach or based on the analysis of genome-wide screening techniques. This review gives an extensive overview of all epigenetic changes described in NB as of today, with a main focus on both prognostic use and the potential of genome-wide techniques to find epigenetic prognostic biomarkers in NB. We summarize the key findings so far and the state-of-the-art of the upcoming methods at a unique time frame in the transition towards combined genome wide chromatin immune-precipitation (ChIP) and DNA sequencing techniques.     

DNA methylation and epigenomics: new technologies and emerging concepts

A report of the Keystone Symposia joint meetings on DNA Methylation and Epigenomics held in Keystone, Colorado, USA, 29 March to 3 April, 2015.     

Secret life of plants: From memory to intelligence

Plants are able to perform photosynthesis and cannot escape from environmental stresses, so they therefore developed sophisticated, highly responsive and dynamic physiology. Others'' and our results indicate that plants solve their optimal light acclimation and immune defenses, photosynthesis and transpiration by a computational algorithm of the cellular automation. Our recent results however suggest that plants are capable of processing information encrypted in light intensity and in its energy. With the help of nonphotochemical quenching and photoelectrophysiological signaling (PEPS) plants are able to perform biological quantum computation and memorize light training in order to optimize their Darwinian fitness. Animals have their network of neuron synapses, electrophysiological circuits and memory, but plants have their network of chloroplasts connected by stromules, PEPS circuits transduced by bundle sheath cells and cellular light memory. It is suggested that plants could be intelligent organisms with much higher organism organization levels than it was thought before.Key words: excess excitation energy, cellular automation, cellular light memory, Darwinian fitness, nonphotochemical quenching, photoelectrophysiological signaling, SAA, SAR     

Aging and epigenetics: longitudinal changes in gene-specific DNA methylation

DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.     

Encoded evidence: DNA in forensic analysis

Sherlock Holmes said "it has long been an axiom of mine that the little things are infinitely the most important", but never imagined that such a little thing, the DNA molecule, could become perhaps the most powerful single tool in the multifaceted fight against crime. Twenty years after the development of DNA fingerprinting, forensic DNA analysis is key to the conviction or exoneration of suspects and the identification of victims of crimes, accidents and disasters, driving the development of innovative methods in molecular genetics, statistics and the use of massive intelligence databases.     

Cancer epigenetics: from mechanism to therapy

The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15 years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it is time to embrace the central role of epigenetics in cancer.     

From genes to machines: DNA nanomechanical devices

The structural properties that enable DNA to serve so effectively as genetic material can also be used for other purposes. The complementarity that leads to the pairing of the strands of the DNA double helix can be exploited to assemble more complex motifs, based on branched structures. These structures have been used as the basis of larger 2D and 3D constructions. In addition, they have been used to make nanomechanical devices. These devices range from DNA-based shape-shifting structures to gears and walkers, a DNA-stress gauge and even a translation device. The devices are activated by mechanisms as diverse as small molecules, proteins and, most intriguingly, other molecules of DNA.