Complexity of Mammalian Transcription

The next generation sequencing technologies are profoundly influencing our way to study biology. We have previously developed cap-analysis gene expression (CAGE) to simultaneously mRNA/noncoding RNA starting sites and simultaneously detect their expression. Altogether, CAGE achieves comprehensive coverage of transcription starting site and allows to assign newly discovered promoters/5' ends to the rest of the RNA sequence (CAGEscan technology). With these technologies, we can infer the transcriptional networks that regulate gene expression. This technology is being applied to a broad range of samples to elucidate the promotome and the regulatory networks of mouse and human primary cells and tissues in the FANTOM5 project. DeepCAGE allows also detecting dynamic expression of repeat elements, which show peculiar expression patterns and provide alternative promoters and functional genome elements. We have also used deepCAGE on subcellular fractions as a part of the ENCODE project. We have detected clear patterns of expression of retrotransposon elements (RE) in a panel of human and mouse tissues, which are likely to have a regulatory role. Now, we have clearly identified specific patterns of non-coding RNAs and other RE-derived RNA in different cell compartments, with a particular interesting role of LINE elements, which seem to be preferentially bound to the chromatin. Other retrotransposon elements, like LTRs, are prevalently expressed in ES and iPS cells, where they may have a role to keep the stem cells undifferentiated. Altogether, these data are pointing at a potential function of the retrotransposon elements and other ncRNAs to regulate the epigenome.