Characterization of circular RNAs in human, mouse and rat hearts.

Deep sequencing techniques and advanced data analysis methods recently enabled the characterization of thousands of circular RNA isoforms (circRNAs) from a number of tissues and organisms. There is emerging evidence that some circRNAs may have important biological functions or serve as diagnostic biomarkers in disease conditions. In order to analyze circRNA expression in the heart and its changes in different conditions we performed RNA-Seq analysis of ribosome-depleted libraries from rats (neonatal and adult), mice (sham or after transverse aortic constriction, TAC) and humans (failing, non-failing). All samples were sequenced after a treatment with exonuclease RNase R or a mock treatment and >9000 candidate circRNAs were detected for each species. Additionally, we performed separate isolation of nuclear and cytoplasmic RNA and co-immunoprecipitated RNA interacting with endogenous argonaute 2 (Ago2) in primary cardiac myocytes. We found circRNAs to be significantly enriched in the cytoplasm compared to linear transcripts and to have a similar level of association with Ago2. Notably in all three species we observed dozens of circRNAs arising from the titin (Ttn) gene, which is known to undergo highly complex alternative splicing during heart maturation. Correspondingly we observed extensive differential regulation of Ttn circRNAs between neonatal and adult rat hearts, suggesting that circRNA formation could be involved in the regulation of titin splicing. We expect that our inventory of cardiac circRNAs, as well as the information on their conservation and differential expression will provide an important basis for further studies addressing their function and suitability as biomarkers

Galaxy HiCExplorer: a web server for reproducible Hi-C data analysis, quality control and visualization

Galaxy HiCExplorer is a web server that facilitates the study of the 3D conformation of chromatin by allowing Hi-C data processing, analysis and visualization. With the Galaxy HiCExplorer web server, users with little bioinformatic background can perform every step of the analysis in one workflow: mapping of the raw sequence data, creation of Hi-C contact matrices, quality assessment, correction of contact matrices and identification of topological associated domains (TADs) and A/B compartments. Users can create publication ready plots of the contact matrix, A/B compartments, and TADs on a selected genomic locus, along with additional information like gene tracks or ChIP-seq signals. Galaxy HiCExplorer is freely usable at: https://hicexplorer.usegalaxy.eu and is available as a Docker container: https://github.com/deeptools/docker-galaxy-hicexplorer

Epigenetics: At the crossroads between genetic and environmental determinants of disease

Epigenetic modifications play an essential role in the functional regulation of genes, including their expression. In contrast to the relative stability of the genome, the epigenome varies in a very dynamic way, through what are known as epigenetic mechanisms. These epigenetic modifications are reversible and are conditioned by environmental pressures. The most well-known epigenetic DNA modifications are the methylation of the cytosines present in the context of cytosine-guanine dinucleotides and the posttranslational modification of histones. Several works have reported that events in the early environment are associated with changes in gene expression and biological function and that such changes persist beyond the immediate influence of the stimulus and into adulthood. While the exact molecular mechanisms underlying developmental programming are largely unknown, there is much epidemiological evidence and data from animal studies linking epigenetic modifications with parental lifestyle (e.g., alcohol or tobacco consumption), nutrition, and environmental factors (such as exposure to UV light or heavy metals and stress). Moreover, pre-existing pathologies in the parents (e.g., diabetes, obesity, or metabolic syndrome) can also increase the susceptibility of the offspring to developing certain diseases over the course of their lifetime.Peer reviewe