In situ hybridizations of single-copy GC-rich, gene-rich and GC-poor, gene-poor chicken DNA allowed us to localize the gene-rich and the gene-poor chromosomal regions in interphase nuclei of cold-blooded vertebrates. Our results showed that the gene-rich regions from amphibians (Rana esculenta) and reptiles (Podarcis sicula) occupy the more internal part of the nuclei, whereas the gene-poor regions occupy the periphery. This finding is similar to that previously reported in warm-blooded vertebrates, in spite of the lower GC levels of the gene-rich regions of cold-blooded vertebrates. This suggests that this similarity extends to chromatin structure, which is more open in the gene-rich regions of both mammals and birds and more compact in the gene-poor regions. In turn, this may explain why the compositional transition undergone by the genome at the emergence of homeothermy did not involve the entire ancestral genome but only a small part of it, and why it involved both coding and noncoding sequences. Indeed, the GC level increased only in that part of the genome that needed a thermodynamic stabilization, namely in the more open gene-rich chromatin of the nuclear interior, whereas the gene-poor chromatin of the periphery was stabilized by its own compact structure.
BackgroundFolic acid and its derivates, known as folates, are chemoprotective micronutrients of great interest because of their essential role in the maintenance of health and genomic integrity. The supplementation of folic acid during pregnancy has long been known to reduce the risk of neural tube defects (NTDs) in the foetus. Folate metabolism can be altered by many factors, including adequate intake through diet. Folate deficiency can compromise the synthesis, repair and methylation of DNA, with deleterious consequences on genomic stability and gene expression. These processes are known to be altered in chronic diseases, including cancer and cardiovascular diseases.Main bodyThis review focuses on the association between folate intake and the risk of childhood leukaemia. Having compiled and analysed studies from the literature, we show the documented effects of folates on the genome and their role in cancer prevention and progression with particular emphasis on DNA methylation modifications. These changes are of crucial importance during pregnancy, as maternal diet has a profound impact on the metabolic and physiological functions of the foetus and the susceptibility to disease in later life. Folate deficiency is capable of modifying the methylation status of certain genes at birth in both animals and humans, with potential pathogenic and tumorigenic effects on the progeny. Pre-existing genetic polymorphisms can modify the metabolic network of folates and influence the risk of cancer, including childhood leukaemias. The protective effects of folic acid might be dose dependent, as excessive folic acid could have the adverse effect of nourishing certain types of tumours.ConclusionOverall, maternal folic acid supplementation before and during pregnancy seems to confer protection against the risk of childhood leukaemia in the offspring. The optimal folic acid requirements and supplementation doses need to be established, especially in conjunction with other vitamins in order to determine the most successful combinations of nutrients to maintain genomic health and wellbeing. Further research is therefore needed to uncover the role of maternal diet as a whole, as it represents a main factor capable of inducing permanent changes in the foetus.
The chicken karyotype, like that of the vast majority of avian species, shows a large number of dot-shaped microchromosomes that are characterized, like most telomeric regions of the macrochromosomes, by the highest GC levels and the highest gene densities. In interphase nuclei, these gene-dense regions are centrally located, and are characterized by an open chromatin structure (a similar situation also exists in mammals). Avian species belonging to the Accipitridae family (diurnal raptors) show a karyotype with no very large chromosomes, and with only a very small number of microchromosomes. To identify the GC-rich (and gene-rich) regions of the chromosomes and nuclei from Accipitridae, we performed heterologous in-situ hybridizations using chicken GC-richest isochores as probes. Our results clearly show that the gene-rich regions are prevalently located in the few microchromosome pairs and in the telomeric regions of the middle-sized chromosomes, as well as in the interior of the interphase nuclei. This result is consistent with a common organization of the genome in the nuclei of warm-blooded vertebrates. Indeed, in spite of the different size and morphology of the chromosomes, the gene-dense regions are always located in the interior of the nuclei.
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