FISH-eyed and genome-wide views on the spatial organisation of gene expression

Eukaryotic cells store their genome inside a nucleus, a dedicated organelle shielded by a double lipid membrane. Pores in these membranes allow the exchange of molecules between the nucleus and cytoplasm. Inside the mammalian cell nucleus, roughly 2 m of DNA, divided over several tens of chromosomes is packed. In addition, protein and RNA molecules functioning in DNA-metabolic processes such as transcription, replication, repair and the processing of RNA fill the nuclear space. While many of the nuclear proteins freely diffuse and display a more or less homogeneous distribution across the nuclear interior, some appear to preferentially cluster and form foci or bodies. A non-random structure is also observed for DNA: increasing evidence shows that selected parts of the genome preferentially contact each other, sometimes even at specific sites in the nucleus. Currently a lot of research is dedicated to understanding the functional significance of nuclear architecture, in particular with respect to the regulation of gene expression. Here we will evaluate evidence implying that the folding of DNA is important for transcriptional control in mammals and we will discuss novel high-throughput techniques expected to further boost our knowledge on nuclear organisation.