Gene activity is not only determined by processes occurring very close to or at the gene, such as transcription factor or RNA Polymerase II (PolII) binding. A multitude of past observations such as the localization of inactive chromatin to the nuclear periphery and active chromatin in the centre of the nucleus, the clustering of highly transcribed genes at transcriptional hotspots as well as the looping of active genes out of the chromosome territory made clear that the 'context matters' and the 3-dimensional organization of the chromatin fibre is fundamental for genome function. Here we want to review whether and how the different architectural levels that were recently identified by high-throughput chromatin conformation capturing techniques influence transcription.